Genmab and AbbVie confirmed the Phase 3 EPCORE DLBCL-1 trial did not meet its U.S. primary endpoint after epcoritamab failed to significantly improve overall survival versus standard chemoimmunotherapy in relapsed or refractory diffuse large B-cell lymphoma.
Written By: Anshu Gupta, PharmD
Reviewed By: Pharmacally Editorial Team
Genmab and AbbVie have clarified that overall survival (OS) was the only U.S. primary endpoint in the Phase 3 EPCORE DLBCL-1 trial evaluating subcutaneous epcoritamab monotherapy in adults with relapsed or refractory diffuse large B-cell lymphoma (DLBCL) who were ineligible for autologous stem cell transplantation. Because the study did not show a statistically significant improvement in OS compared with standard chemoimmunotherapy, it did not meet its U.S. primary endpoint.
The clarification follows the companies’ January 2026 topline announcement and presentation of additional data at the European Hematology Association (EHA) 2026 Congress. Genmab stated that the multinational trial incorporated region-specific primary endpoints, with overall survival serving as the sole primary endpoint for U.S. regulatory evaluation.
EPCORE DLBCL-1 Missed the U.S. Overall Survival Endpoint
EPCORE DLBCL-1 (NCT04628494) is a global, randomized, open-label, multicenter Phase 3 trial comparing epcoritamab monotherapy with investigator’s choice of chemoimmunotherapy in adults with relapsed or refractory DLBCL who were not eligible for high-dose chemotherapy and autologous stem cell transplantation.
Patients in the control arm received either rituximab plus gemcitabine and oxaliplatin (R-GemOx) or bendamustine plus rituximab (BR), reflecting commonly used treatment options in this difficult-to-treat population.
Although the study included prespecified primary endpoints that varied across geographic regions, Genmab and AbbVie confirmed that overall survival was the only primary endpoint evaluated in the United States. The trial failed to demonstrate a statistically significant improvement in OS, meaning it did not achieve its U.S. primary objective.
The companies said detailed findings from the study will be submitted for publication in a peer-reviewed medical journal.
Epcoritamab Remains Available Under Accelerated FDA Approval
The Phase 3 outcome does not alter the current U.S. regulatory status of epcoritamab, which remains available under the FDA’s Accelerated Approval pathway for adults with relapsed or refractory diffuse large B-cell lymphoma, not otherwise specified, including DLBCL arising from indolent lymphoma and high-grade B-cell lymphoma after two or more prior lines of systemic therapy.
The CD3xCD20 bispecific antibody is marketed as EPKINLY® in the United States and Japan and TEPKINLY® in the European Union. The therapy has received regulatory approvals in selected lymphoma indications across more than 65 territories.
Bispecific T-Cell Engager Targets CD3 and CD20
Epcoritamab is an IgG1 bispecific antibody developed using Genmab’s proprietary DuoBody® platform. The therapy simultaneously binds CD3 on T cells and CD20 on malignant B cells, triggering T-cell-mediated destruction of CD20-positive lymphoma cells. Unlike intravenous bispecific antibodies, epcoritamab is administered subcutaneously.
The drug is being jointly developed by Genmab and AbbVie under their oncology collaboration. The companies share commercialization responsibilities in the United States and Japan, while AbbVie leads commercialization in other global markets.
Development Continues Across Earlier Treatment Settings
Despite the EPCORE DLBCL-1 result, development of epcoritamab continues across multiple lymphoma settings.
Topline data from the Phase 3 EPCORE DLBCL-4 study evaluating a chemotherapy-free combination of fixed-duration epcoritamab and lenalidomide in relapsed or refractory DLBCL have already been disclosed. Meanwhile, results from the Phase 3 EPCORE DLBCL-2 trial, which is evaluating fixed-duration epcoritamab plus standard R-CHOP in patients with newly diagnosed DLBCL, are expected later in 2026.
Diffuse large B-cell lymphoma accounts for approximately one-quarter to one-third of all non-Hodgkin lymphoma cases worldwide and remains an aggressive malignancy with limited treatment options for patients whose disease relapses or becomes refractory after prior therapy. The ongoing epcoritamab development program will help determine whether the bispecific antibody can provide greater benefit in earlier treatment settings or in combination regimens despite the negative overall survival outcome observed in EPCORE DLBCL-1.
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About the Writer
Anshu Gupta (LinkedIn) is a PharmD professional and healthcare writer with interests in clinical research, pharmacovigilance, regulatory affairs, and medical writing. She has presented research at academic conferences and completed certifications in Good Clinical Practice (GCP), ICH-GCP, and drug safety. Passionate about clinical trials and evidence-based medicine, she is committed to translating scientific evidence into accurate, reliable, and accessible healthcare content.