Epcoritamab Enhances Progression-Free Survival vs SOC in R/R DLBCL

The subcutaneous administration of epcoritamab (Epkinly) displayed progression-free survival (PFS) and objective response rate (ORR) benefits but did not confer a significant overall survival (OS) benefit compared with standard-of-care (SOC) therapy among patients with relapsed/refractory diffuse large B-cell lymphoma (DLBCL) in the phase 3 EPCORE DLBCL-1 trial (NCT04628494), according to a news release from the developer, Genmab.¹

Specifically, treatment with the bispecific T-cell engager exhibited an HR of 0.74 (95% CI, 0.60-0.92) for PFS vs SOC therapy in this patient group. Additionally, the HR for OS was 0.96 (95% CI, 0.77-1.20). Moreover, improvements in complete response (CR) rate, duration of response (DOR), and time to next treatment were observed with epcoritamab among this DLBCL population.

Moreover, adverse effects (AEs) seen in the phase 3 study were consistent with the known safety profile of the investigational agent, and data assessing the potential impact of factors including the COVID-19 pandemic will be submitted for presentation at future medical meetings. The developers plan to re-engage with global regulatory authorities to determine next steps for this agent among patients with relapsed/refractory DLBCL.

“The EPCORE DLBCL-1 trial is the first phase 3 study evaluating a bispecific antibody monotherapy to demonstrate improvements in [PFS] in patients with relapsed or refractory DLBCL,” Jan van de Winkel, PhD, chief executive officer of Genmab, a developer of epcoritamab, said in the news release.¹ “The results from this global trial contribute to the growing body of evidence supporting epcoritamab and build upon the robust foundation established by epcoritamab, which has been used to treat thousands of patients in need of additional therapeutic options. Together with our partner, AbbVie, we remain deeply committed to advancing the development of epcoritamab as a potential core therapy across a broad range of B-cell malignancies.”

The phase 3 trial enrolled 483 patients treated with at least 1 prior line of therapy, including 73% treated with 2 or more prior lines, who were ineligible for high-dose chemotherapy and autologous stem cell transplantation (HDT-ASCT). Those who underwent treatment received epcoritamab monotherapy or investigator’s choice of SOC therapy, which included gemcitabine/oxaliplatin (R-GemOx) or bendamustine (Treanda) plus rituximab (Rituxan).

Those treated with epcoritamab received the agent once weekly for the first 3 months, followed by every other week for 6 months, and once every 28-day cycle until disease progression or unacceptable AEs.² Those who received SOC chemotherapy received R-GemOx on days 1 and 15 or days 1, 2, 15, and 16 every 28 days for 4 months or bendamustine/rituximab on days 1 and 2 for each 3-week cycle for up to 4.5 months.

The primary end point of the trial was OS. Secondary end points included PFS, ORR, DOR, time to response, minimal residual disease–negative duration, and safety.

Additionally, 2 additional phase 3 trials evaluating fixed-duration epcoritamab among patients with DLBCL are ongoing, with data anticipated in 2026. The EPCORE DLBCL-2 trial (NCT05578976) is evaluating frontline epcoritamab plus rituximab, cyclophosphamide, doxorubicin hydrochloride, vincristine, and prednisone (R-CHOP); the EPCORE DLBCL-4 trial (NCT06508658) is evaluating epcoritamab/lenalidomide (Revlimid) vs chemoimmunotherapy in the relapsed/refractory DLBCL population.

Inclusion criteria in the phase 3 EPCORE DLBCL-1 trial included having DLBCL not otherwise specified, “double-hit” or “triple-hit” DLBCL, as well as other T-cell/histiocyte-rich LBCLs, and progression following or ineligibility for previous HDT-ASCT. An ECOG performance status of 0 or 2, acceptable renal and liver function, and a life expectancy of at least 2 months on SOC were also requirements for study eligibility.

References

1. Genmab announces topline results for epcoritamab (DuoBody® CD3xCD20) from phase 3 EPCORE® DLBCL-1 trial in patients with relapsed/refractory diffuse large B-cell lymphoma (DLBCL). News release. Genmab. January 19, 2026. Accessed January 19, 2026. https://tinyurl.com/38w547bv
2. A phase 3 Trial of epcoritamab vs investigator's choice chemotherapy in relapsed/​refractory (R/​R) diffuse large B-cell lymphoma (DLBCL) (EPCORE DLBCL-1). ClinicalTrials.gov. Updated January 7, 2026. Accessed January 19, 2026. https://tinyurl.com/yjbx55wm