Genmab and AbbVie's Epcoritamab Misses Overall Survival Goal in Key Phase 3 Trial for Relapsed DLBCL

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Danish biotech Genmab and U.S. partner AbbVie announced on January 16, 2026, that their bispecific antibody epcoritamab failed to demonstrate a statistically significant improvement in overall survival in a late-stage trial for patients with relapsed or refractory diffuse large B-cell lymphoma (DLBCL). The EPCORE DLBCL-1 study involved 483 patients ineligible for stem cell transplant, comparing epcoritamab monotherapy to standard investigator’s choice therapies. Despite positive signals in progression-free survival, the overall survival hazard ratio of 0.96 (95% CI 0.77-1.20) did not meet significance, prompting discussions with regulators on next steps.

Trial Design and Key Findings

The Phase 3 EPCORE DLBCL-1 trial randomized patients with relapsed or refractory DLBCL who had received at least one prior therapy and were unsuitable for high-dose chemotherapy followed by autologous stem cell transplant. About 73% of participants had two or more prior lines of treatment. Epcoritamab, marketed as Epkinly in the U.S. and Tepkinly in the EU, was tested as monotherapy against rituximab plus gemcitabine/oxaliplatin (R-GemOx) or rituximab plus bendamustine.

Primary endpoint progression-free survival (PFS) improved significantly with epcoritamab, showing a hazard ratio of 0.74 (95% CI 0.60-0.92). Secondary endpoints included higher complete response rates, longer duration of response, and delayed time to next treatment. Safety aligned with the drug’s known profile, featuring cytokine release syndrome mostly low-grade. Genmab CEO Jan van de Winkel highlighted it as “the first Phase 3 study evaluating a bispecific antibody monotherapy to demonstrate improvements in PFS in R/R DLBCL patients.”

Background on Epcoritamab and DLBCL

Diffuse large B-cell lymphoma represents the most common aggressive non-Hodgkin lymphoma, affecting over 18,000 new patients annually in the U.S. alone, with relapse rates around 30-40% after first-line therapy. Epcoritamab, a subcutaneous CD3xCD20 bispecific T-cell engager, activates the patient’s immune system to target CD20-positive B-cells, offering convenience over IV alternatives.

Already approved for third-line relapsed/refractory large B-cell lymphomas in multiple regions, epcoritamab generated strong early data in Phase 1/2 trials like EPCORE NHL-1. This trial builds on that, targeting a harder-to-treat population ineligible for salvage therapy and transplant. Genmab’s pipeline emphasizes bispecifics, with epcoritamab as a cornerstone alongside recent positives in follicular lymphoma.

Expert Commentary

Oncologists note the mixed results temper enthusiasm but affirm PFS gains’ value. “While overall survival is the gold standard, meaningful PFS extensions can delay disease progression and improve quality of life in this frail group,” said Dr. Maria Lim, a lymphoma specialist at Memorial Sloan Kettering Cancer Center, not involved in the study. She emphasized bispecifics’ role in bridging to other therapies.

Dr. John P. Leonard from Weill Cornell Medicine added, “The lack of OS benefit isn’t surprising given crossover effects and subsequent treatments; full data at conferences will clarify subgroups benefiting most.” Adverse events remained manageable, with no new signals, supporting its tolerability over chemo. Experts anticipate regulatory filings for PFS label expansions.

Public Health Implications

This outcome underscores challenges in advancing second-line options for transplant-ineligible DLBCL patients, who face median survival under 12 months post-relapse. Epcoritamab’s PFS benefit could expand access to targeted immunotherapy, reducing reliance on toxic chemo regimens like R-GemOx. With approvals in over 50 countries for later lines, label expansions might reach more patients sooner.

Genmab shares dropped over 7% post-announcement, reflecting investor caution on OS, yet the firm eyes 2026 data from EPCORE DLBCL-2 (frontline combo) and others. For patients, it signals immunotherapy’s promise but highlights trial endpoints’ nuances—PFS often precedes OS in oncology. Clinicians may integrate it earlier pending labels.

Limitations and Future Directions

The open-label design risks bias, though randomization mitigates it; interim OS analysis may mature later. Patient heterogeneity, including prior CAR-T exposure, could dilute effects. No OS crossover adjustment was mentioned, potentially underestimating benefit.

Companies plan regulatory talks and medical meeting presentations for full data. Upcoming trials test fixed-duration dosing and combos like with Revlimid, potentially unlocking OS gains. Balanced against successes like 79% PFS risk reduction in follicular lymphoma, this reinforces iterative oncology development.

Medical Disclaimer: This article is for informational purposes only and should not be considered medical advice. Always consult with qualified healthcare professionals before making any health-related decisions or changes to your treatment plan. The information presented here is based on current research and expert opinions, which may evolve as new evidence emerges.