Epcoritamab/R2 Earns European Approval for R/R Follicular Lymphoma

The European Commission has granted marketing authorization for epcoritamab-bysp (Epkinly; Tepkinly) in combination with lenalidomide (Revlimid) and rituximab (Rituxan; R2) for adult patients with relapsed/refractory follicular lymphoma, according to a news release from the developer, AbbVie.¹ The combination is the only bispecific-based therapy approved in Europe for follicular lymphoma in the second-line setting.

The approval is based on the phase 3 EPCORE FL-1 trial (NCT05409066), an open-label study that randomly assigned patients with relapsed/refractory follicular following at least 1 prior line of therapy to fixed-duration epcoritamab plus R2 (n = 243) or R2 alone (n = 245). Patients received epcoritamab in 28-day cycles for up to 12 cycles or until disease progression or unacceptable toxicity.

According to findings presented at the 2025 American Society of Hematology (ASH) Annual Meeting and Exposition, the epcoritamab combination reduced the risk of disease progression or death by 79% compared with R2 alone (HR, 0.21; 95% CI, 0.13-0.33; P <.0001).² The overall response rate (ORR) was 96% (95% CI, 90.2%-98.6%) with the epcoritamab combination vs 81% (95% CI, 72.7%-87.7%) with R2 alone (P <.0001). The complete response (CR) rate was 74% (95% CI, 68.5%-79.8%) with epcoritamab plus R2, compared with 43% (95% CI, 37.0%-49.7%) with R2 alone.

The safety profile of the combination was consistent with the known profiles of epcoritamab and R2 individually. The most common adverse reactions occurring in at least 20% of patients included neutropenia, rash, upper respiratory tract infections, fatigue, diarrhea, injection site reactions, and anemia. Serious adverse reactions occurred in 44% of patients, most commonly cytokine release syndrome (CRS), pneumonia, COVID-19 infection, and febrile neutropenia, each in at least 5% of patients.

“Follicular lymphoma is a persistent form of cancer that remains incurable, which means patients need more treatment options,” Catherine Thieblemont, MD, PhD, head of the Hemato-Oncology Department at Hôpital Saint-Louis, Assistance Publique-Hôpitaux de Paris, said in the release.¹ “The results shown in the EPCORE FL-1 trial are clinically meaningful, demonstrating the potential for [epcoritamab] plus R2 to change the treatment paradigm for patients, offering the chance at a durable response with a chemotherapy-free option.”

The open-label trial was conducted to assess the safety and efficacy of rituximab and lenalidomide with or without epcoritamab in patients with relapsed/refractory follicular lymphoma. Patients were assigned to receive 375 mg/m² of intravenous rituximab for up to five 28-day cycles and 20 mg of oral lenalidomide for up to 12 cycles with or without subcutaneous injections of epcoritamab for up to 12 cycles.³ Epcoritamab was given at 48 mg using a step-up dosing regimen to the full dose in cycle 1.

The coprimary end points of the phase 3 protocol included ORR and progression-free survival. Secondary end points included CR rate, overall survival, minimal residual disease negativity rate, duration of response, and time to progression.

Epcoritamab, marketed as Epkinly in the US and Japan and Tepkinly in the European Union, is a bispecific antibody built on Genmab's DuoBody platform that binds CD3 on T cells and CD20 on B cells to direct T-cell-mediated killing of malignant B cells. The FDA approved the epcoritamab/R2-based regimen for this relapsed/refractory population in November 2025.⁴

“There remains a critical need for new treatment options to improve outcomes for patients with relapsed/refractory follicular lymphoma, particularly in earlier lines of therapy,” Roopal Thakkar, MD, executive vice president of research and development and chief scientific officer at AbbVie, stated in the release.¹ “This approval is important because it brings an effective treatment option to patients across Europe.”

References

1. AbbVie announces TEPKINLY® (epcoritamab) in combination with lenalidomide and rituximab is approved by the European Commission for the treatment of relapsed or refractory follicular lymphoma. News release. AbbVie. July 6, 2026. Accessed July 6, 2026. https://tinyurl.com/2u9x5y3f
2. Falchi L, Nijland M, Huang H, et al. Primary phase 3 results from the EPCORE- FL-1 trial of epcoritamab with rituximab and lenalidomide (R2) versus R2 for relapsed or refractory follicular lymphoma. Blood. 2025;146(supplement 1):466. doi:10.1182/blood-2025-466
3. Study of subcutaneous epcoritamab in combination with intravenous rituximab and oral lenalidomide (R2) to assess adverse events and change in disease activity in adult participants with follicular lymphoma (EPCORE FL-1). ClincialTrials.gov. Updated July 28, 2025. Accessed July 6, 2026. https://tinyurl.com/254t76mu
4. FDA approves epcoritamab-bysp for follicular lymphoma indications. News release. FDA. November 18, 2025. Accessed July 6, 2026. https://tinyurl.com/4utb74x3