Primary results from the global, randomised, Phase III EPCORE DLBCL-1 (EudraCT 2020-003016-27) trial were presented at the European Hematology Association (EHA) 2026 Congress, held on 11–14 June in Stockholm, Sweden. Sponsored by Genmab and AbbVie, the study compared Epkinly (epcoritamab) monotherapy, a subcutaneous CD3×CD20 bispecific antibody, against investigator’s choice chemoimmunotherapy (CIT), either rituximab plus gemcitabine/oxaliplatin or rituximab plus bendamustine.

The trial enrolled 483 patients with relapsed/refractory large B-cell lymphoma (R/R LBCL), all of whom were autologous stem-cell transplant (ASCT)-ineligible or relapsed after ASCT, with one prior line of therapy or more, representing a population with poor outcomes and significant unmet need. The dual primary endpoints were progression-free survival (PFS) and overall survival (OS), with at least one required to be met.

With a median follow-up of 43.2 and 42.3 months in the experimental and control arms, respectively, Epkinly met the PFS endpoint with a hazard ratio (HR) of 0.74 (95% confidence interval [CI] 0.60–0.92; p=0.0059) and a 24-month PFS of 30% versus 13% for CIT. Epkinly also delivered a higher complete response (CR) rate than CIT (38% versus 26%), longer median duration of complete response (DoR) (not reached (NR) versus 10.8 months), and time to next treatment (6.6 versus 4.3 months). Objective response rate (ORR) was comparable in the Epkinly and CIT arms (51% versus 48%), and OS was not significantly different between the two groups (HR 0.96; 95% CI 0.77–1.20).

The investigators attributed this to two confounders. First, enrolment was concentrated during the Covid-19 pandemic, specifically when the Omicron variant was widespread, and fatalities due to Covid-19 occurred in 9% of the Epkinly arm versus 3% in the control arm. Second, there was an imbalance in post-progression treatment, as an effective subsequent therapy like bispecifics, chimeric antigen receptor (CAR) T-cell therapy, or stem-cell transplant was used more often in the CIT arm than the Epkinly arm (31% versus 6%). A post-hoc analysis adjusting for both factors moved the OS HR to 0.76 (95% CI, 0.59–0.99), favouring Epkinly. EPCORE DLBCL-1 is the first randomised, Phase III trial in which a CD3×CD20 bispecific, given as a single agent rather than in combination, improved PFS over CIT in R/R LBCL. This could support moving Epkinly into the second line. However, since the efficacy results met only one of the two endpoints, Genmab will discuss next steps with global regulatory authorities. Whether the post-hoc adjustment will be enough to convince the US Food and Drug Administration (FDA) remains uncertain. The FDA's August 2025 draft guidance on assessing OS will add pressure. It frames OS as both an efficacy and safety endpoint, using it to flag therapies that improve response while adding toxicity, and it pushes sponsors to designate OS as the primary endpoint wherever feasible. Under that lens, the safety read is also nuanced for Epkinly. Monotherapy Epkinly might be expected to be gentler than chemotherapy, yet the experimental arm showed higher rates of grade 3–4 infections than the control arm (30% versus 12%) and grade 5 treatment-emergent adverse events (17% versus 6%). These were attributed to far longer exposure (mean 11 months versus 2 months) and to the Covid-19 pandemic, not to intrinsic toxicity. On an exposure-adjusted basis, grade 3–4 infections were comparable between the experimental and control arms (4.3 versus 4.9 per 100 patient-months). Notably, febrile neutropenia was reported in 2% of patients in the experimental arm versus 5% of patients in the CIT arm.

Questions remain about whether that is enough to secure approval, and recent precedent in the comparable patient population and the same drug class has raised the stakes. In 2025, the FDA rejected Roche's Columvi (glofitamab) plus chemotherapy in second-line, ASCT-ineligible, R/R LBCL patients, citing that only 9% of trial patients were US-enrolled versus 48% of patients in Asia. The EPCORE DLBCL-1 trial recruited more than 50% of patients in North America/Western Europe. Like Epkinly, Columvi is a CD3×CD20 bispecific and also holds FDA accelerated approval as a third line or later monotherapy.

Given the setback with Columvi and the uncertainty over the FDA's interpretation of the OS data, the chemotherapy backbone may well persist as the official standard of care for this segment. However, Epkinly has another angle beyond monotherapy, as its gemcitabine and oxaliplatin combination (studied in the non-registrational Phase Ib/II EPCORE NHL-2 trial) is already listed as an National Comprehensive Cancer Network (NCCN)-preferred regimen for CAR T-ineligible R/R DLBCL, despite the lack of a formal FDA-approved indication for the combination. Furthermore, the drug is under evaluation across multiple haematological malignancies. The commercial outlook is correspondingly strong, with GlobalData's analyst consensus forecast projecting that Epkinly will have global sales of $2.795bn by 2032.