Epcoritamab R-CHOP delivered a statistically significant and clinically meaningful improvement in progression-free survival (PFS) in newly diagnosed diffuse large B-cell lymphoma (DLBCL), according to topline Phase 3 results announced on October 5, 2026 by AbbVie (NYSE: ABBV) and Genmab A/S (Nasdaq: GMAB). The EPCORE DLBCL-2 trial compared fixed-duration, subcutaneous epcoritamab added to standard rituximab, cyclophosphamide, doxorubicin hydrochloride, vincristine and prednisone (R-CHOP) against R-CHOP alone in patients with an International Prognostic Index (IPI) score of 2 to 5.
The companies said the risk of disease progression or death fell by 51% (HR 0.49 [95% CI 0.36, 0.67]; p-value < 0.0001) in the IPI 2 to 5 population. They described EPCORE DLBCL-2 as the first Phase 3 study of a bispecific antibody combination therapy to show a statistically significant PFS improvement in frontline DLBCL. The safety profile of the combination was reported as generally well tolerated and consistent with the previously reported profiles of epcoritamab and R-CHOP individually.
This was the first planned efficacy interim analysis of the study. Based on the significant benefit, the Independent Data Monitoring Committee (IDMC) recommended unblinding the trial. The Epcoritamab R-CHOP combination remains investigational and is not approved by any regulatory authority, and AbbVie and Genmab said they will engage global regulatory authorities to determine next steps.
AbbVie’s Daejin Abidoye, MD, Vice President, Therapeutic Area Head, Oncology, Solid Tumor and Hematology, said the results suggest the combination could offer “a potential new standard of care” for newly diagnosed patients. Genmab Chief Executive Officer Jan van de Winkel, Ph.D., said the findings could “reshape the frontline treatment landscape,” noting that options for newly diagnosed patients remain limited. These are company statements about potential outcomes and are forward-looking.
Epcoritamab R-CHOP Topline Results: What AbbVie and Genmab Reported
The headline efficacy figure is a 51% reduction in the risk of progression or death. For the IPI 2 to 5 population, the release reports HR 0.49 with a 95% confidence interval of 0.36 to 0.67. For the primary endpoint population, defined as patients with an IPI score of 3 to 5, the release reports the same 51% reduction with HR 0.49 and a 95% confidence interval of 0.35 to 0.69. Both comparisons carry a p-value below 0.0001.
| Data Point | Reported Value |
|---|---|
| Announcement date | October 5, 2026 |
| Sponsors | AbbVie (NYSE: ABBV) and Genmab A/S (Nasdaq: GMAB) |
| Experimental arm | Epcoritamab plus R-CHOP |
| Control arm | R-CHOP alone |
| PFS risk of progression or death, IPI 2 to 5 | 51% reduction; HR 0.49 (95% CI 0.36, 0.67); p < 0.0001 |
| PFS risk of progression or death, IPI 3 to 5 (primary endpoint) | 51% reduction; HR 0.49 (95% CI 0.35, 0.69); p < 0.0001 |
| Analysis type | First planned efficacy interim analysis |
| IDMC recommendation | Unblind the study |
| Median PFS by arm | Not disclosed |
| Overall survival | Not disclosed |
| Response rates | Not disclosed |
| Safety profile | Generally well tolerated; consistent with individual agents |
Several data points were not included in the announcement. The release does not disclose median PFS for either arm, overall survival results, response rates, the number of enrolled patients, or rates of specific adverse events such as cytokine release syndrome. The companies said data will be submitted for presentation at a future medical meeting, so a fuller picture of Epcoritamab R-CHOP efficacy and tolerability should emerge only after that disclosure.
Gilles Salles, MD, PhD, Chief of the Lymphoma Service at Memorial Sloan Kettering Cancer Center, said he served as an investigator in both the landmark trial that established R-CHOP as a standard of care nearly 25 years ago and EPCORE DLBCL-2. He called the 51% reduction clinically meaningful and said the results could be practice-changing and bring the opportunity of cure to more patients. The release discloses that Dr. Salles has financial interests related to AbbVie and Genmab, which readers should weigh.
How Epcoritamab R-CHOP Was Tested: EPCORE DLBCL-2 Design and Eligible Patients
EPCORE DLBCL-2 (NCT05578976) is a global Phase 3, open-label, multicenter, randomized trial evaluating fixed-duration subcutaneous epcoritamab (GEN3013, DuoBody-CD3xCD20) with R-CHOP versus R-CHOP alone in patients with newly diagnosed large B-cell lymphoma. Patients were randomized 2:1. The trial started on February 8, 2023, and is ongoing. The primary endpoint is PFS in participants with an IPI score of 3 to 5, and the key secondary endpoint is PFS in all participants with an IPI score of 2 to 5.
In the Epcoritamab R-CHOP arm, patients receive six cycles of epcoritamab plus R-CHOP followed by two cycles of epcoritamab alone. Patients in the control arm receive six cycles of R-CHOP followed by two cycles of rituximab. The trial enrolled people with 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 large B-cell lymphoma and Epstein-Barr virus-positive DLBCL.
EPCORE DLBCL-2 (NCT05578976) Trial Design
| Parameter | Detail |
|---|---|
| Phase | Phase 3 |
| Design | Global, open-label, multicenter, randomized |
| Randomization | 2:1 |
| Experimental regimen | Epcoritamab plus R-CHOP for six cycles, then epcoritamab alone for two cycles |
| Control regimen | R-CHOP for six cycles, then rituximab for two cycles |
| Population | Newly diagnosed large B-cell lymphoma, IPI score 2 to 5 |
| Primary endpoint | PFS in IPI 3 to 5 |
| Key secondary endpoint | PFS in IPI 2 to 5 |
| Trial start date | February 8, 2023 |
| Status | Ongoing |
| Total enrollment | Not disclosed |
Why Epcoritamab R-CHOP Matters for Newly Diagnosed DLBCL Patients
DLBCL is the most common type of non-Hodgkin lymphoma worldwide, accounting for approximately 25 to 30 percent of cases. In the United States, roughly 25,000 new cases are diagnosed each year. The disease is fast-growing, can arise in lymph nodes or in organs outside the lymphatic system, occurs more often in older people and is slightly more prevalent in men. For many patients, the cancer relapses or becomes refractory, and treatment management remains challenging despite new therapies.
Epcoritamab is an IgG1 bispecific antibody built on Genmab’s DuoBody technology and given subcutaneously. It is designed to bind CD3 on T cells and CD20 on B cells at the same time, inducing T-cell-mediated killing of CD20-positive cells. In the first-line setting, the Epcoritamab R-CHOP result is notable because R-CHOP has been a standard of care for nearly 25 years, according to Dr. Salles’ comments in the release.
Epcoritamab R-CHOP Regulatory Path, EPKINLY Safety Information and Next Steps
No regulatory filing has been announced. AbbVie and Genmab said they will engage global regulatory authorities to determine next steps. Until then, the Epcoritamab R-CHOP combination should be read as an investigational regimen whose safety and efficacy have not been established for this use. Current EPKINLY indications cover relapsed or refractory settings, and the DLBCL indication is approved based on response data, with studies ongoing to confirm clinical benefit.
The release also carries Important Safety Information for EPKINLY as currently approved. Important warnings include cytokine release syndrome (CRS) and neurologic problems, both of which can be serious or fatal, along with serious infections and low blood cell counts. EPKINLY is given on a step-up dosing schedule, and people with DLBCL may be hospitalized after the first full dose on Day 15 of Cycle 1. Side effects can be reported to the FDA through MedWatch or to Genmab US at 1-855-4GENMAB.
EPKINLY (Epcoritamab) Regulatory and Safety Snapshot
| Item | Detail |
|---|---|
| Brand names | EPKINLY (U.S., Japan); TEPKINLY (EU) |
| Approval reach | Certain lymphoma indications in more than 65 countries |
| U.S. indications listed | Relapsed or refractory DLBCL or high-grade B-cell lymphoma after 2 or more treatments; relapsed or refractory FL with lenalidomide and rituximab; relapsed or refractory FL after 2 or more treatments |
| DLBCL approval basis | Patient response data; confirmatory studies ongoing |
| Key warnings | Cytokine release syndrome; neurologic problems; infections; low blood cell counts |
| Hospitalization note | DLBCL patients may be hospitalized after first full dose on Day 15 of Cycle 1 |
| Epcoritamab R-CHOP regulatory status | Investigational; not approved |
| Next step stated | Engage global regulatory authorities |
| Data presentation | To be submitted to a future medical meeting |
