Epcoritamab Misses Sole US Primary End Point of Overall Survival in R/R DLBCL

Epcoritamab-bysp (Epkinly) did not lead to a statistically significant improvement in overall survival (OS) compared with investigator's choice of chemoimmunotherapy (CIT) in patients with relapsed/refractory diffuse large B-cell lymphoma (DLBCL) who were ineligible for autologous stem cell transplantation (ASCT), missing the sole United States (US) primary end point of the phase 3 EPCORE DLBCL-1 trial (NCT04628494), according to a clarification issued by Genmab and AbbVie.¹

In the July 23, 2026, announcement, the companies clarified that EPCORE DLBCL-1 was designed with prespecified primary end points that differed by region and that, in the US—where OS was the sole primary end point—the study did not demonstrate a statistically significant improvement; therefore, it did not meet its primary end point.

Genmab and AbbVie previously reported topline results on January 16, 2026, and presented full data at the 2026 EHA Congress on June 12, 2026, where findings showed that epcoritamab met a dual primary end point of progression-free survival (PFS).^2,3

At EHA 2026, findings showed that at a median follow-up of 38.6 months in the epcoritamab arm and 28.2 months in the CIT arm, the median PFS by independent review committee assessment was 3.5 months (95% CI, 2.9-4.6) with epcoritamab vs 3.0 months (95% CI, 2.9-4.1) with CIT (stratified HR, 0.74; 95% CI, 0.60-0.92; P = .0059).²

The coprimary end point of OS was not significantly different between the arms (stratified HR, 0.96; 95% CI, 0.77-1.20; P = .7285). The complete response (CR) rate was 38% with epcoritamab vs 26% with CIT, and 59% vs 24% of complete responders maintained CR at 36 months, respectively.

Investigators reported that the safety profile of epcoritamab observed in EPCORE DLBCL-1 was consistent with the established safety profile of the agent.

Additional results from EPCORE DLBCL-1 will be submitted for publication in a peer-reviewed medical journal, according to Genmab and AbbVie.¹

“There's a progressive separation of the Kaplan-Meier [PFS] curves, which indicates the depth and durability of the epcoritamab responses compared with [CIT],” Christopher P. Fox, PhD, MBChB(Hons), FRCP, FRCPath, said during a presentation of the EPCORE DLBCL-1 data at the 2026 EHA Congress.²

Fox is a clinical professor of hematology in the Faculty of Medicine & Health Sciences at the University of Nottingham and an honorary consultant hematologist and lymphoma lead at Nottingham University Hospitals National Health Service Trust in the United Kingdom.

How was the EPCORE DLBCL-1 trial designed?

EPCORE DLBCL-1 was a global, open-label, multicenter, randomized phase 3 trial evaluating subcutaneous epcoritamab vs investigator's choice of CIT—either rituximab (Rituxan) plus gemcitabine and oxaliplatin (R-GemOx) or bendamustine plus rituximab (BR)—in patients with R/R DLBCL who are ineligible for high-dose therapy with ASCT (HDT-ASCT).^1,2

The trial enrolled patients with CD20-positive relapsed/refractory large B-cell lymphoma, including de novo and transformed disease, double-hit/triple-hit DLBCL, grade 3B follicular lymphoma, and T-cell/histiocyte-rich large B-cell lymphoma. Patients were required to receive at least 1 prior line of systemic therapy, have an ECOG performance status no higher than 2. Ineligibility for or relapse after HDT-ASCT was also required.²

A total of 483 patients were randomly assigned 1:1 to subcutaneous epcoritamab at 48 mg in 28-day cycles until disease progression or intolerable toxicity (n = 241) or investigator's choice of CIT (n = 242), with R-GemOx selected for 174 patients and BR for 68 patients.

The dual primary end points were PFS by independent review committee per Lugano criteria and OS, with OS serving as the only primary end point in the US.^1,2 Secondary end points included overall response rate, CR rate, duration of response, time to next treatment, and safety.² The trial began on January 13, 2021, and is ongoing.¹

Epcoritamab, a subcutaneously administered CD3xCD20 bispecific antibody, is approved under the FDA's accelerated approval pathway for adults with R/R DLBCL, not otherwise specified, including DLBCL arising from indolent lymphoma, and high-grade B-cell lymphoma, after 2 or more lines of systemic therapy.¹

Genmab and AbbVie are continuing to evaluate the agent across the DLBCL treatment landscape; topline results from the phase 3 EPCORE DLBCL-4 trial showed that fixed-duration epcoritamab plus lenalidomide significantly improved PFS vs R-GemOx in patients with R/R DLBCL who had received at least 1 prior line of therapy.⁴

References

1. Genmab and AbbVie provide clarification on phase 3 EPCORE DLBCL-1 trial evaluating epcoritamab (DuoBody-CD3xCD20) in patients with relapsed/refractory diffuse large B-cell lymphoma (DLBCL). News release. Genmab and AbbVie. July 23, 2026. Accessed July 24, 2026. https://www.businesswire.com/news/home/20260723712759/en/Genmab-and-AbbVie-Provide-Clarification-on-Phase-3-EPCORE-DLBCL-1-Trial-Evaluating-Epcoritamab-DuoBody-CD3xCD20-in-Patients-with-RelapsedRefractory-Diffuse-Large-B-cell-Lymphoma-DLBCL
2. Fox CP, Inchiappa L, Ferhanoğlu B, et al. Results from EPCORE DLBCL-1: randomized phase 3 study of epcoritamab vs investigator's choice chemoimmunotherapy in patients with relapsed/refractory large B-cell lymphoma. Abstract presented at: European Hematology Association 2026 Congress; June 11-14, 2026; Stockholm, Sweden. Abstract S235.
3. Epcoritamab significantly improves PFS vs chemoimmunotherapy in R/R large B-cell lymphoma. OncLive. Published June 13, 2026. Accessed July 24, 2026. https://www.onclive.com/view/epcoritamab-significantly-improves-pfs-vs-chemoimmunotherapy-in-r-r-large-b-cell-lymphoma
4. Epcoritamab plus lenalidomide improves PFS vs R-GemOx in R/R DLBCL. OncLive. Published June 30, 2026. Accessed July 24, 2026. https://www.onclive.com/view/epcoritamab-plus-lenalidomide-improves-pfs-vs-r-gemox-in-r-r-dlbcl