The European Commission has approved Tepkinly in combination with lenalidomide and rituximab for adults with relapsed or refractory follicular lymphoma after at least two prior systemic therapies, based on Phase 3 EPCORE FL-1 data showing a 79% reduction in risk of disease progression or death — marking the first bispecific antibody-based combination regimen approved in Europe for this indication.
AbbVie and Genmab announced today that the EC has granted marketing authorization for epcoritamab (brand name Tepkinly) in combination with lenalidomide and rituximab (R2) for the treatment of adult patients with relapsed or refractory (R/R) follicular lymphoma (FL) who have received at least two prior systemic therapies.¹ The approval makes epcoritamab plus R2 the first and only bispecific antibody-based combination therapy authorized by the EC for this indication, and follows the US FDA approval of the same regimen in November 2025. The decision is based on pivotal Phase 3 EPCORE FL-1 data published in The Lancet in January 2026,² which demonstrated a statistically significant and clinically meaningful improvement across both primary endpoints versus standard of care R2 alone.
EPCORE FL-1 (NCT05409066) is a global, open-label, randomized phase 3 trial enrolling 488 patients with R/R FL across 189 centers in 30 countries, randomized 1:1 to epcoritamab plus R2 or R2 alone.² At a median follow-up of 14.8 months, epcoritamab plus R2 reduced the risk of disease progression or death by 79% compared with R2 alone (HR 0.21; 95% CI: 0.14–0.31; p<0.0001), with median progression-free survival not yet reached in the epcoritamab arm versus 11.7 months with R2.¹ The overall response rate was 96% with epcoritamab plus R2 versus 81% with R2 alone, with complete response rates of 74% versus 38%, respectively.¹ Subgroup analyses presented at the European Hematology Association (EHA) Annual Congress in June 2026 confirmed consistent treatment benefit across all clinically relevant patient subgroups.³
Epcoritamab plus R2 was administered as a fixed-duration regimen — a clinically meaningful feature for patients with an incurable but often slowly progressing disease, where limiting cumulative treatment burden matters. The safety profile was consistent with the known profiles of the individual agents, with cytokine release syndrome (CRS) the most common adverse event of interest; the majority of CRS events were grade 1 or 2, manageable with step-up dosing and standard premedication protocols.²
"The EPCORE FL-1 results demonstrate the potential of epcoritamab, in combination with established therapies, to enable earlier intervention across sites of care and deliver improved outcomes for patients with relapsed or refractory follicular lymphoma."
— Judith Klimovsky, MD, executive vice president and chief development officer, Genmab
Epcoritamab is a subcutaneous CD3×CD20 IgG1 bispecific antibody developed using Genmab's proprietary DuoBody technology.¹ It simultaneously engages CD20-expressing malignant B cells and CD3-expressing T cells, redirecting cytotoxic T cells to recognize and destroy lymphoma cells — a mechanism that operates independently of the adaptive immune priming required by conventional checkpoint inhibitors, and that works regardless of prior CD20 monoclonal antibody exposure.⁴ The subcutaneous route of administration is a practical advantage over intravenously administered bispecifics in follicular lymphoma, supporting more flexible outpatient delivery.
The combination with R2 is mechanistically well-grounded: lenalidomide enhances T-cell activation and immune synapse formation, amplifying the cytotoxic signal delivered by epcoritamab, while rituximab contributes complementary CD20-directed tumor cell depletion through antibody-dependent cellular cytotoxicity and complement-dependent mechanisms.² Preclinical data showed that epcoritamab's T-cell redirecting activity is preserved in the presence of rituximab, with no evidence of antagonistic interaction between the agents.²
As Elizabeth Budde, hematologic oncologist and associate professor at City of Hope, noted in a BioPharm International report on the EC approval of mosunetuzumab — the first CD20×CD3 bispecific approved in this setting — "It is exciting to have a new class of immunotherapy like [a bispecific], offering a readily available, chemotherapy-free, and fixed-duration treatment." That paradigm has now advanced substantially with the EPCORE FL-1 data, which demonstrate superiority over the existing chemotherapy-free standard of care rather than single-arm activity alone.
Follicular lymphoma is the second most common form of non-Hodgkin lymphoma globally, accounting for approximately 20% of all NHL diagnoses and affecting more than 28,000 new patients in Europe annually.⁵ Although most patients respond to first-line chemoimmunotherapy, nearly all eventually relapse, and outcomes worsen with each successive line of therapy. The 2L+ setting has historically been addressed with re-treatment using chemotherapy-based regimens, with deepening toxicity and shortening response durations over time.
The approval of epcoritamab plus R2 adds a chemotherapy-free combination option to a 2L+ setting that already includes mosunetuzumab (Lunsumio), the first CD20×CD3 bispecific approved in Europe for FL, which received conditional EC authorization in 2022 for patients after two or more prior lines of therapy.⁵ Epcoritamab's differentiation lies in the combination regimen and the randomized Phase 3 evidence base — EPCORE FL-1 is the first Phase 3 trial to demonstrate superiority of a bispecific-containing regimen over R2 in R/R FL, providing a level of evidence that single-arm registrational studies cannot match.
"The EPCORE FL-1 results demonstrate the potential of epcoritamab, in combination with established therapies, to enable earlier intervention across sites of care and deliver improved outcomes for patients with relapsed or refractory follicular lymphoma," said Judith Klimovsky, MD, Executive Vice President and Chief Development Officer of Genmab. "We remain committed to developing epcoritamab as a potential core therapy for B-cell malignancies."¹
