Genmab and AbbVie: Epcoritamab + R‑CHOP cuts progression risk 51% in frontline DLBCL Phase 3
- EPCORE DLBCL-2 showed epcoritamab plus R-CHOP reduced risk of disease progression or death by 51% (HR 0.49 [95% CI 0.36, 0.67]; p < 0.0001).
- The study is described as the first Phase 3 bispecific antibody combination to demonstrate a statistically significant PFS improvement in frontline DLBCL.
- Randomized 2:1 trial enrolled patients with IPI scores 2–5 (includes DLBCL subtypes) and compared six cycles of R-CHOP plus fixed‑duration subcutaneous epcoritamab (then two cycles epcoritamab) versus R-CHOP then two cycles rituximab; trial started 8 Feb 2023 (NCT05578976) and is ongoing.
- The combination was generally well tolerated and consistent with previously reported safety profiles; Genmab and AbbVie will engage global regulators and submit data for presentation; the combination remains investigational.
Topline result
The Phase 3 EPCORE DLBCL-2 trial demonstrated that subcutaneous epcoritamab in combination with standard R-CHOP produced a statistically significant and clinically meaningful improvement in progression-free survival in newly diagnosed diffuse large B-cell lymphoma (DLBCL) patients with an International Prognostic Index (IPI) score of 2 to 5. The risk of disease progression or death was reduced by 51% (HR 0.49 [95% CI 0.36, 0.67]; p < 0.0001). The companies described this as the first Phase 3 study of a bispecific antibody combination to show a frontline PFS benefit in DLBCL.
Trial design
EPCORE DLBCL-2 is a global, open-label, randomized 2:1 Phase 3 trial comparing fixed-duration subcutaneous epcoritamab plus R-CHOP to R-CHOP alone in patients with newly diagnosed large B-cell lymphoma (IPI 2–5). Patients received six cycles of R-CHOP with epcoritamab followed by two cycles of epcoritamab, or six cycles of R-CHOP followed by two cycles of rituximab. The trial enrolled DLBCL, 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 EBV-positive DLBCL. The primary endpoint was PFS in participants with IPI 3–5 and a key secondary endpoint was PFS in the total IPI 2–5 population; the trial started on February 8, 2023 and is ongoing (NCT05578976).
Safety and next steps
The safety profile of epcoritamab combined with R-CHOP was reported as generally well tolerated and consistent with previously reported safety profiles of the individual agents. Genmab and AbbVie said they will engage global regulatory authorities, submit the data for presentation at a future medical meeting, and determine next steps. The epcoritamab plus R-CHOP combination remains investigational and is not approved by regulatory authorities.
Source: Genmab