Epcoritamab/Lenalidomide Significantly Improves PFS in R/R DLBCL

Treatment with fixed-duration epcoritamab-bysp (Epkinly) plus lenalidomide (Revlimid) produced a statistically significant and clinically meaningful improvement in progression-free survival (PFS) compared with chemoimmunotherapy in patients with relapsed/refractory diffuse large B-cell lymphoma (DLBCL), meeting the primary end point of the phase 3 EPCORE DLBCL-4 trial (NCT06508658), according to topline results announced in a news release by AbbVie.¹

The risk of disease progression or death was reduced by 60% (HR, 0.40; 95% CI, 0.30-0.55; P <.0001) and 56% (HR, 0.44; 95% CI, 0.33-0.60; P <.0001) with the epcoritamab combination compared with rituximab (Rituxan) plus gemcitabine and oxaliplatin (R-GemOx), based on differing censoring rules applied in the US and outside the US, respectively. The safety profile of the epcoritamab combination was consistent with the previously reported safety profiles of the individual agents.

"Despite recent advances, there remains a critical need for innovative therapies to improve outcomes for those battling DLBCL, an aggressive and often difficult-to-treat cancer," said Daejin Abidoye, MD, vice president and therapeutic area head of Oncology, Solid Tumor and Hematology at AbbVie, in the news release.¹ "Today’s encouraging topline results highlight the potential of epcoritamab, a fixed-treatment therapy, in combination with lenalidomide, as a meaningful treatment option after initial disease progression.”

EPCORE DLBCL-4 is a global, open-label, randomized, phase 3 trial evaluating epcoritamab, a T-cell engaging bispecific antibody administered subcutaneously, in combination with lenalidomide compared with R-GemOx in adult patients with [relapsed/refractory] LBCL.² Eligible histologies include DLBCL not otherwise specified, high-grade B-cell lymphoma with MYC and BCL2 and/or BCL6 rearrangements, follicular lymphoma grade 3B, T-cell/histiocyte-rich LBCL, and EBV-positive DLBCL.

Patients 18 years and older were required to have received at least 1 prior line of treatment, including a CD20-targeted monoclonal antibody-containing combination chemotherapy regimen; to have experienced failure or relapse after, or not been a candidate for, autologous stem cell transplantation; and to have been ineligible for or unable to receive CAR T-cell therapy since their DLBCL diagnosis. An ECOG performance score of 0 to 2 and a life expectancy of more than 3 months were additional criteria for enrollment.

Exclusion criteria included any evidence of primary central nervous system (CNS) lymphoma or known CNS involvement at screening. Additionally, those with any documented refractoriness to lenalidomide were ineligible for inclusion on the trial.

Patients were randomly assigned to receive subcutaneous epcoritamab plus oral lenalidomide for up to twelve 28-day cycles, or R-GemOx for up to 4 cycles.

The primary end point of the trial was PFS. Secondary end points included complete response rate, overall survival, and minimal residual disease-negativity rate.

"These topline results add to the growing evidence supporting the versatility of epcoritamab-based combinations, including fixed-duration epcoritamab, across lines of therapy for patients with relapsed or refractory [LBCL] who received at least 1 prior treatment," said Jan van de Winkel, PhD, president and chief executive officer of Genmab, in a separate release by Genmab.³ "With each new combination and treatment setting, we are building on our vision for epcoritamab as a core therapy across B-cell malignancies."

AbbVie and Genmab plan to engage global regulatory authorities to discuss next steps for the epcoritamab/lenalidomide combination, with full data from EPCORE DLBCL-4 to be submitted for presentation at a future medical meeting.

These findings follow topline results from the phase 3 EPCORE DLBCL-1 trial (NCT04628494), which previously showed that epcoritamab monotherapy improved PFS compared with investigator’s choice of chemoimmunotherapy in a similar relapsed/refractory DLBCL population, supporting the ongoing development of epcoritamab-based regimens across multiple treatment settings and lines of therapy in LBCL.⁴

References

1. AbbVie announces positive phase 3 results for epcoritamab plus lenalidomide in patients with relapsed or refractory diffuse large B-cell lymphoma. News release. AbbVie. June 29, 2026. Accessed June 30, 2026. https://tinyurl.com/abbvie-epcore-dlbcl4
2. A study of subcutaneous epcoritamab in combination with lenalidomide compared with R-GemOx in participants with R/R DLBCL (EPCORE DLBCL-4). ClinicalTrials.gov. Updated April 8, 2026. Accessed June 30, 2026. https://clinicaltrials.gov/study/NCT06508658
3. Genmab announces positive phase 3 results for epcoritamab plus lenalidomide in patients with relapsed/refractory diffuse large B-cell lymphoma, demonstrating statistically significant improvement in progression-free survival. News release. Genmab A/S. June 29, 2026. Accessed June 30, 2026. https://tinyurl.com/genmab-epcore-dlbcl4
4. 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 June 30, 2026. https://tinyurl.com/38w547bv