- EPKINLY plus rituximab and lenalidomide (EPKINLY + R2) is now the first and only bispecific antibody combination therapy available for patients with relapsed or refractory follicular lymphoma after at least one line of systemic therapy
- In the Phase 3 EPCORE® FL-1 trial, EPKINLY + R2 demonstrated significantly superior progression-free survival and overall response rates compared to standard of care R2 with approximately 3 out of 4 patients achieving a complete response
- Approval marks third indication for EPKINLY and first-ever FDA approval for a bispecific combination therapy in lymphoma
NORTH CHICAGO, Ill., Nov. 18, 2025 /PRNewswire/ -- AbbVie (NYSE: ABBV) today announced that EPKINLY® (epcoritamab-bysp), a T-cell engaging bispecific antibody administered subcutaneously, in combination with rituximab and lenalidomide (EPKINLY + R2) is approved by the U.S. Food and Drug Administration (FDA) for the treatment of adult patients with relapsed or refractory (R/R) follicular lymphoma (FL). This approval of EPKINLY is based on results from the pivotal Phase 3 EPCORE® FL-1 study that evaluated fixed duration EPKINLY + R2 compared to standard of care R2 and demonstrates the potential of this combination therapy to reshape FL treatment and to reach patients earlier in their treatment.i
"Recurrent follicular lymphoma can be an incurable, complex and persistent disease, creating a clear need for additional treatments that can change its course earlier in the treatment journey," said Lorenzo Falchi, M.D., lymphoma specialist, department of medicine, Memorial Sloan Kettering Cancer Center. "The results shown with EPKINLY + R2 in the EPCORE FL-1 study are incredibly meaningful, demonstrating durable responses compared to patients treated with R2 alone. These data, delivered by a regimen that's chemotherapy-free and can be administered in the outpatient setting, suggest that EPKINLY + R2 could potentially become a new standard of care."
FL is typically an indolent (slow-growing) form of non-Hodgkin lymphoma (NHL) that arises from B-lymphocytes and impacts approximately 15,000 new patients per year in the U.S.ii,iii The disease is considered incurable with current available therapies.iv Patients with FL often relapse, and in some cases, the disease can transform into a more aggressive form of NHL called diffuse large B-cell lymphoma (DLBCL).v
The Phase 3 EPCORE FL-1 study included a broad range of patients, including those with indolent to aggressive disease. In the study, EPKINLY + R2 reduced the risk of disease progression or death by 79% (HR 0.21, 95% CI: 0.13% - 0.33%, p<0.0001) compared to standard of care R2 alone. In the dual primary endpoint of overall response rate (ORR), 89% of patients treated with EPKINLY + R2 responded to treatment (n=216/243, 95% CI: 84% - 93%; p<0.0001) compared to 74% of patients treated with R2 (n=181/245, 95% CI: 68%-79%). The median for dual primary endpoint of progression-free survival (PFS), was not reached (NR) among patients treated with EPKINLY + R2 (95% CI: 21.9 months - NR) compared to 11.2 months for patients treated with R2 (95% CI: 10.5 months - NR). Among patients who were treated with EPKINLY + R2, 74% achieved a complete response (CR) (n=181/243, 95% CI: 69% - 80%, p<0.0001) compared to 43% of patients treated with R2 (n=106/245, 95% CI: 37% - 50%).i
The safety profile of EPKINLY + R2 in the EPCORE FL-1 study was generally consistent with the known safety profiles of the individual regimens (epcoritamab and R2). The most common (≥ 20%) adverse reactions in patients who received EPKINLY + R2 were rash, upper respiratory tract infections, fatigue, injection site reactions, constipation, diarrhea, cytokine release syndrome (CRS), pneumonia, COVID-19 and fever. The most common Grade 3 to 4 laboratory abnormalities (≥ 10%) were decreased neutrophil count, lymphocyte count, and platelets. CRS occurred in 24% of patients at the recommended 3 step-up dosage schedule, and was primarily low grade (19% Grade 1, 5% Grade 2). A single event of immune effector cell-associated neurotoxicity syndrome (ICANS) occurred in one patient, grade 1 (0.8%). The prescribing information has a Boxed Warning for serious or life-threatening CRS and ICANS. Warnings and precautions include infections, cytopenias, and embryo-fetal toxicity. Please see additional Important Safety Information below.
"Today's milestone marks meaningful progress for people living with follicular lymphoma. With a bispecific-based therapy that can be administered in a variety of medical settings, patients have the possibility of accessing this treatment at sites of care closer to where they live," said Meghan Gutierrez, chief executive officer, Lymphoma Research Foundation.
EPKINLY + R2 was previously granted Breakthrough Therapy Designation (BTD) by the FDA for the treatment of R/R FL. This designation is an FDA process designed to expedite the development and review of drugs that are intended to treat a serious condition, and preliminary clinical evidence indicates that the drug may demonstrate substantial improvement over available therapy on a clinically significant endpoint(s).
"With this approval, EPKINLY is now the first bispecific antibody available for patients with follicular lymphoma in the second-line plus setting. New options are needed to improve outcomes for patients with relapsed or refractory disease," said Daejin Abidoye, MD, vice president, therapeutic area head, oncology, solid tumor and hematology, AbbVie.
In June 2024, EPKINLY monotherapy was granted accelerated approval by the FDA for the treatment of R/R FL following two or more lines of systemic therapy. With the results of the confirmatory Phase 3 EPCORE FL-1 study, the FDA has also converted this accelerated approval to a full approval. Both companies will pursue additional international regulatory approvals for the R/R FL indication.
Data from the Phase 3 EPCORE FL-1 study will be presented at the Annual Meeting and Exposition of the American Society of Hematology (ASH) in December 2025.
About the EPCORE® FL-1 Trial
EPCORE FL-1 (NCT05409066) is a Phase 3 open-label randomized interventional trial to evaluate the safety and efficacy of epcoritamab plus rituximab and lenalidomide (R2) versus R2 alone in patients with relapsed/refractory (R/R) follicular lymphoma (FL). Patients were randomized to receive EPKINLY in combination R2 (n=243) or R2 alone (n=245). Patients received EPKINLY in 28-day cycles for a total of 12 cycles or until disease progression or unacceptable toxicity, whichever occurred first. Efficacy was established based on the dual primary endpoints of progression free survival (PFS) and overall response rate (ORR) determined by Lugano 2014 criteria as assessed by Independent Review Committee (IRC). Additional efficacy outcome measures include complete response (CR) and duration of response (DOR).
About EPKINLY® (epcoritamab-bysp)
EPKINLY® (epcoritamab-bysp) is an IgG1-bispecific antibody created using Genmab's proprietary DuoBody® technology and administered subcutaneously. Genmab's DuoBody-CD3 technology is designed to direct cytotoxic T cells selectively to elicit an immune response toward target cell types. Epcoritamab is designed to simultaneously bind to CD3 on T cells and CD20 on B cells and induces T-cell-mediated killing of CD20+ cells.vi
Epcoritamab (approved under the brand name EPKINLY in countries including the U.S. and Japan, and as TEPKINLY® in the European Union) has received regulatory approval in certain lymphoma indications in more than 65 countries. Epcoritamab is being co-developed by Genmab and AbbVie as part of the companies' oncology collaboration. The companies will share commercialization responsibilities in the U.S. and Japan, with AbbVie responsible for further global commercialization. Both companies will pursue additional international regulatory approvals for the R/R FL indication and additional approvals for the R/R DLBCL indication.
Genmab and AbbVie continue to evaluate the use of epcoritamab as a monotherapy, and in combination, across lines of therapy in a range of hematologic malignancies. This includes four additional ongoing Phase 3, open-label, randomized trials including a trial evaluating epcoritamab as a monotherapy in patients with R/R DLBCL compared to investigators choice immunochemotherapy (NCT04628494), a trial evaluating epcoritamab in combination with R-CHOP in adult patients with newly diagnosed DLBCL (NCT05578976), a trial evaluating epcoritamab in combination with rituximab and lenalidomide (R2) compared to chemoimmunotherapy in patients with previously untreated FL (NCT06191744), and a trial evaluating epcoritamab in combination with lenalidomide compared to chemotherapy infusion in patients with R/R DLBCL (NCT06508658). The safety and efficacy of epcoritamab has not been established for these investigational uses. Please visit www.clinicaltrials.gov for more information.
About AbbVie in Oncology
AbbVie is committed to elevating standards of care and bringing transformative therapies to patients worldwide living with difficult-to-treat cancers. We are advancing a dynamic pipeline of investigational therapies across a range of cancer types in both blood cancers and solid tumors. We are focusing on creating targeted medicines that either impede the reproduction of cancer cells or enable their elimination. We achieve this through various, targeted treatment modalities and biology interventions, including small molecule therapeutics, antibody-drug conjugates (ADCs), immuno-oncology-based therapeutics, multispecific antibody and novel CAR-T platforms. Our dedicated and experienced team joins forces with innovative partners to accelerate the delivery of potential breakthrough medicines.
Today, our expansive oncology portfolio comprises approved and investigational treatments for a wide range of blood cancers and solid tumors. We are evaluating more than 35 investigational medicines in multiple clinical trials across some of the world's most widespread and debilitating cancers. As we work to have a remarkable impact on people's lives, we are committed to exploring solutions to help patients obtain access to our cancer medicines.
About AbbVie
AbbVie's mission is to discover and deliver innovative medicines and solutions that solve serious health issues today and address the medical challenges of tomorrow. We strive to have a remarkable impact on people's lives across several key therapeutic areas including immunology, oncology, neuroscience and eye care – and products and services in our Allergan Aesthetics portfolio.
i EPKINLY (epcoritamab-bysp) [package insert]. Copenhagen, Denmark: Genmab, 2025.
ii Lymphoma Research Foundation official website. https://lymphoma.org/aboutlymphoma/nhl/fl/. Accessed November 2025.
iii Leukemia & Lymphoma Society. https://www.lls.org/research/follicular-lymphoma-fl. Accessed November 2025.
iv Ghione P, Palomba ML, Ghesquieres H, et al. Treatment patterns and outcomes in relapsed/refractory follicular lymphoma: results from the international SCHOLAR-5 study. Haematologica. 2023;108(3):822-832. doi: 10.3324/haematol.2022.281421.
v Al-Tourah AJ, Gill KK, Chhanabhai M, et al. Population-based analysis of incidence and outcome of transformed non-Hodgkin's lymphoma. J Clin Oncol. 2008 Nov 10;26(32):5165-9. doi: 10.1200/JCO.2008.16.0283. Epub 2008 Oct 6. PMID: 18838711.
vi Engelberts PJ, et al. DuoBody-CD3xCD20 Induces Potent T-Cell-Mediated Killing of Malignant B Cells in Preclinical Models and Provides Opportunities for Subcutaneous Dosing. EBioMedicine. 2020;52:102625. doi: 10.1016/j.ebiom.2019.102625.