Epcoritamab/R-CHOP Shows PFS Benefit in Newly Diagnosed DLBCL

Adding fixed-duration epcoritamab-bysp (Epkinly) to standard rituximab (Rituxan), cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) significantly improved progression-free survival (PFS) vs R-CHOP alone in patients with newly diagnosed diffuse large B-cell lymphoma (DLBCL) in the phase 3 EPCORE DLBCL-2 trial (NCT05578976), according to a news release from AbbVie and Genmab.¹

What were the topline results of the EPCORE DLBCL-2 trial?

In the trial, the primary end point was PFS among patients with an IPI score of 3 to 5. In this population, epcoritamab plus R-CHOP reduced the risk of progression or death by 51% vs R-CHOP alone (HR, 0.49; 95% CI, 0.35-0.69; P <.0001). Results were consistent for the key secondary end point of PFS in all patients with an IPI score of 2 to 5 (HR, 0.49; 95% CI, 0.36-0.67; P <.0001).

The findings came from the first planned interim efficacy analysis. After that analysis, an independent data monitoring committee recommended unblinding the study. The safety profile of the combination was consistent with the known profiles of epcoritamab and R-CHOP individually. Full data will be submitted for presentation at a future medical meeting, and the developers plan to engage global regulatory authorities.

"The 51% reduction in the risk of progression or death is clinically meaningful and highly relevant to everyday practice," said Gilles Salles, MD, PhD, chief of the Lymphoma Service and holder of the Steven A. Greenberg Chair at Memorial Sloan Kettering Cancer Center, in the press release.¹

What is the EPCORE DLBCL-2 trial design?

The global, open-label, multicenter EPCORE DLBCL-2 trial enrolled patients with newly diagnosed large B-cell lymphoma and an IPI score of 2 to 5. Eligible histologies were:

• DLBCL not otherwise specified
• high-grade B-cell lymphoma with MYC and BCL2 and/or BCL6 rearrangements
• grade 3B follicular lymphoma
• T-cell/histiocyte-rich large B-cell lymphoma
• Epstein-Barr virus–positive DLBCL

Patients were randomly assigned 2:1 to one of 2 regimens: one group received subcutaneous epcoritamab plus R-CHOP for 6 cycles, followed by 2 cycles of epcoritamab alone; the other received R-CHOP for 6 cycles, followed by 2 cycles of rituximab. The trial began enrolling in February 2023 and is ongoing.

How did epcoritamab perform in relapsed/refractory DLBCL?

The frontline readout follows topline results from the phase 3 EPCORE DLBCL-1 trial (NCT04628494).² Investigators compared epcoritamab monotherapy with investigator's choice of rituximab plus gemcitabine and oxaliplatin or bendamustine (Treanda) plus rituximab. They enrolled 483 patients with relapsed/refractory DLBCL who were ineligible for high-dose chemotherapy and autologous stem cell transplant, and 73% had received at least 2 prior lines of therapy.³

According to topline results announced in January 2026, epcoritamab improved PFS (HR, 0.74; 95% CI, 0.60-0.92). It also improved complete response rate, duration of response, and time to next treatment. However, overall survival did not differ significantly between arms (HR, 0.96; 95% CI, 0.77-1.20). In the release on the EPCORE DLBCL-1 trial data, the developers stated that further analysis was ongoing, including the potential effects of the COVID-19 pandemic and the increasing availability of novel antilymphoma therapies.

What is epcoritamab's regulatory history?

Epcoritamab is a subcutaneously administered IgG1 bispecific antibody that binds CD3 on T cells and CD20 on B cells, inducing T cell–mediated killing of CD20-positive cells. It has received regulatory approval for certain lymphoma indications in more than 65 countries.

In the US, epcoritamab is approved for relapsed/refractory DLBCL or high-grade B-cell lymphoma after at least 2 lines of therapy. That approval was granted based on response data, and confirmatory studies are ongoing. The FDA also approved epcoritamab with lenalidomide (Revlimid) and rituximab for relapsed/refractory follicular lymphoma in November 2025 based on data from the phase 3 EPCORE FL-1 trial (NCT05409066).⁴ At the same time, it granted traditional approval for epcoritamab monotherapy in follicular lymphoma after at least 2 prior lines of therapy. Epcoritamab plus R-CHOP remains investigational in newly diagnosed DLBCL.

References

1. AbbVie and Genmab announce epcoritamab in combination with R-CHOP demonstrates significant improvement in progression-free survival versus R-CHOP in patients with newly diagnosed diffuse large B-cell lymphoma. News release. AbbVie and Genmab A/S. October 5, 2026. Accessed October 5, 2026. https://tinyurl.com/5kcyfxhb
2. 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 A/S. January 16, 2026. Accessed October 5, 2026. https://tinyurl.com/3bku563x
3. A phase 3 trial of epcoritamab vs investigator's choice chemotherapy in R/R DLBCL (EPCORE DLBCL-1). ClinicalTrials.gov. Updated May 22, 2026. Accessed October 5, 2026. https://tinyurl.com/44fudtjp
4. FDA approves epcoritamab-bysp for follicular lymphoma indications. News release. FDA. November 18, 2025. Accessed October 5, 2026. https://tinyurl.com/4pejyct8