Phase 3 EPCORE DLBCL‑4 shows epcoritamab plus lenalidomide significantly improves progression‑free survival versus R‑GemOx in relapsed/refractory DLBCL, reducing risk of progression or death by up to 60%.
Written By: Kirti Kumbhar, M. Pharm (QA)
Reviewed By: Pharmacally Editorial Team
AbbVie has reported positive topline results from the Phase 3 EPCORE DLBCL-4 (NCT06508658) trial, showing that epcoritamab combined with lenalidomide significantly improved progression-free survival (PFS) compared with rituximab, gemcitabine, and oxaliplatin (R-GemOx) in adults with relapsed or refractory diffuse large B-cell lymphoma (DLBCL) who had received at least one prior line of therapy.
The study met its primary endpoint at the prespecified analysis, demonstrating a statistically significant and clinically meaningful reduction in the risk of disease progression or death. Depending on regional censoring rules, the combination reduced the risk of progression or death by 60% (HR 0.40; 95% CI 0.30–0.55; p<0.0001) under U.S. analysis criteria and 56% (HR 0.44; 95% CI 0.33–0.60; p<0.0001) outside the United States.
Chemotherapy-Free Approach Targets an Unmet Need
Diffuse large B-cell lymphoma is the most common form of aggressive non-Hodgkin lymphoma. Although many patients respond to first-line therapy, a substantial proportion relapse or develop refractory disease, leaving limited treatment options for those who are ineligible for autologous stem cell transplantation or CAR-T cell therapy.
Epcoritamab is a subcutaneous IgG1 bispecific antibody developed using Genmab’s DuoBody technology. The therapy simultaneously binds CD3 on T cells and CD20 on B cells, triggering T-cell-mediated destruction of malignant CD20-positive B cells. The drug is already approved as EPKINLY in several countries, including the United States and Japan, and as TEPKINLY in the European Union for selected lymphoma indications.
EPCORE DLBCL-4 Demonstrated Significant Clinical Benefit
The global, open-label, randomized Phase 3 trial enrolled adults with relapsed or refractory large B-cell lymphoma, including DLBCL and other aggressive B-cell lymphoma subtypes. Eligible patients had previously received anti-CD20-containing chemotherapy and had relapsed after treatment or were unsuitable for autologous stem cell transplantation and unable or ineligible to receive CAR-T therapy.
Patients received subcutaneous epcoritamab weekly during cycles 1-3, followed by dosing every four weeks through cycle 12, together with oral lenalidomide (25 mg daily on days 1-21 of each 28-day cycle). The control group received intravenous R-GemOx for up to four treatment cycles.
The safety profile of the combination remained consistent with the established safety profiles of epcoritamab and lenalidomide, with no new safety signals reported in the topline analysis.
Commenting on the findings, Daejin Abidoye, MD, Vice President and Therapeutic Area Head for Oncology, Solid Tumor and Hematology at AbbVie, said the results highlight the potential of fixed-duration epcoritamab combined with lenalidomide to provide a meaningful treatment option for patients whose disease progresses after initial therapy and who continue to face poor clinical outcomes.
Regulatory Discussions Planned
AbbVie and Genmab plan to engage global regulatory authorities to discuss potential submissions based on the Phase 3 results. The companies also intend to present detailed findings at a future scientific meeting.
Beyond DLBCL, the partners continue to evaluate epcoritamab as both monotherapy and combination therapy across multiple hematologic malignancies. Ongoing studies will further define its role across different treatment settings as development of the CD3×CD20 bispecific antibody continues.
What This Means for Patients
The Phase 3 results suggest that epcoritamab combined with lenalidomide may offer a new chemotherapy-free treatment option for people with relapsed or refractory diffuse large B-cell lymphoma (DLBCL) whose disease has returned after previous treatment. The combination significantly delayed disease progression compared with a commonly used chemotherapy regimen while maintaining a safety profile consistent with the known effects of both medicines. Although the therapy is not yet approved for this indication, AbbVie and Genmab plan to discuss these results with regulators, bringing the combination one step closer to becoming a potential new treatment option for eligible patients.
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About the Writer
Kirti Kumbhar (LinkedIn) is an M.Pharm graduate with experience in Quality Assurance at Lupin Limited and a strong interest in clinical research, regulatory affairs, and Trial Master File (TMF) management. She has developed knowledge of regulatory documentation, quality systems, compliance, and healthcare research through her professional experience. Passionate about clinical development and continuous learning, Kirti is committed to supporting high-quality healthcare documentation, regulatory excellence, and research-driven healthcare advancements.