Genmab Wins European Commission Approval for TEPKINLY® Combination
Genmab A/S has announced that the European Commission (EC) has granted marketing authorization for TEPKINLY® (epcoritamab) in combination with lenalidomide and rituximab (R2) for the treatment of adult patients with relapsed or refractory (R/R) follicular lymphoma (FL). The approval marks an important milestone in the treatment landscape for one of the most common forms of indolent non-Hodgkin lymphoma, providing physicians and patients across the European Union with a new chemotherapy-free treatment option designed to deliver durable clinical responses.
The regulatory decision is based on results from the pivotal Phase 3 EPCORE® FL-1 clinical trial, which demonstrated that the combination of TEPKINLY with lenalidomide and rituximab significantly improved clinical outcomes compared with the current standard-of-care regimen consisting of lenalidomide and rituximab alone. The findings showed substantial improvements in progression-free survival, overall response rates, and complete response rates, highlighting the potential of the combination to redefine treatment approaches for patients experiencing disease relapse.
The approval further expands the clinical role of TEPKINLY, strengthening its position within Genmab’s growing hematology portfolio and reinforcing the company’s strategy of developing innovative immunotherapies for B-cell malignancies.
Addressing an Ongoing Need in Follicular Lymphoma
Follicular lymphoma is a slow-growing cancer of B lymphocytes and represents the second most common subtype of non-Hodgkin lymphoma worldwide. The disease accounts for approximately 20% to 30% of all non-Hodgkin lymphoma diagnoses and is particularly prevalent among European populations, where its incidence is significantly higher than in many other regions of the world.
Although advances in therapy have improved patient outcomes over recent decades, follicular lymphoma remains an incurable disease. Most patients initially respond well to treatment; however, the disease almost inevitably returns over time. Each relapse often presents new treatment challenges, as subsequent remissions generally become shorter and therapeutic options become increasingly limited.
For patients with relapsed or refractory disease, physicians continue to seek therapies capable of producing deep and durable responses while minimizing treatment-related toxicity.
The European Commission’s approval of TEPKINLY in combination with lenalidomide and rituximab addresses this significant unmet need by introducing an effective chemotherapy-free regimen earlier in the treatment journey.
TEPKINLY Builds on Innovative Immunotherapy
TEPKINLY (epcoritamab) is a bispecific antibody designed to engage the body’s immune system in the fight against cancer.
Unlike conventional therapies, epcoritamab simultaneously binds CD3 receptors on T cells and CD20 proteins expressed on malignant B cells. This dual-targeting mechanism brings immune cells into direct contact with lymphoma cells, enabling T cells to recognize and destroy cancerous B lymphocytes.
Because the therapy harnesses the patient’s own immune system, it represents an important advancement in the expanding field of immuno-oncology.
The latest approval broadens TEPKINLY’s clinical utility by combining this immune-mediated mechanism with two well-established lymphoma therapies—lenalidomide, an immunomodulatory agent, and rituximab, a CD20-targeted monoclonal antibody.
Together, the combination seeks to maximize immune activation while improving long-term disease control.
Phase 3 EPCORE FL-1 Trial Demonstrated Significant Clinical Benefit
The European Commission based its decision on findings from the pivotal Phase 3 EPCORE FL-1 study, an international open-label clinical trial evaluating the efficacy and safety of TEPKINLY plus lenalidomide and rituximab compared with lenalidomide and rituximab alone in adults with relapsed or refractory follicular lymphoma.
The trial produced highly encouraging efficacy results across multiple clinically meaningful endpoints.
One of the most significant findings was a 79% reduction in the risk of disease progression or death among patients receiving the TEPKINLY combination.
The study reported a hazard ratio of 0.21, with a 95% confidence interval ranging from 0.13 to 0.33 and a highly statistically significant p-value of less than 0.0001.
These results indicate a substantial improvement in progression-free survival compared with the existing standard-of-care regimen.
High Overall Response Rates
The study also demonstrated remarkable improvements in tumor response.
Among patients treated with TEPKINLY in combination with lenalidomide and rituximab, the overall response rate reached 96%.
This compares with an overall response rate of 81% among patients receiving lenalidomide and rituximab alone.
The difference was statistically significant and further supports the enhanced antitumor activity achieved through addition of epcoritamab.
High response rates are particularly important in relapsed follicular lymphoma because achieving disease control after relapse often becomes progressively more difficult as patients undergo successive lines of therapy.
Improved Complete Response Rates
Perhaps even more notable were the improvements observed in complete responses.
Nearly three-quarters of patients receiving the TEPKINLY combination achieved complete remission.
Specifically, 74% of patients experienced a complete response compared with 43% of patients receiving standard therapy alone.
Complete responses are generally associated with deeper disease eradication and frequently translate into longer remission durations.
The large difference observed between treatment groups suggests the combination may offer more durable disease control than currently available options.
Safety Profile Consistent with Previous Experience
Investigators reported that the safety profile observed during the EPCORE FL-1 trial was generally consistent with the known safety characteristics of the individual treatment components.
The most frequently reported adverse events included neutropenia, rash, upper respiratory tract infections, fatigue, diarrhea, injection-site reactions, anemia, constipation, thrombocytopenia, cytokine release syndrome, hypogammaglobulinemia, COVID-19 infection, fever, and pneumonia.
As expected for immune-based therapies, cytokine release syndrome represented one of the notable treatment-related events observed during the study.
Overall, serious adverse reactions occurred in approximately 44% of patients receiving the TEPKINLY combination.
The most common serious adverse events included cytokine release syndrome, pneumonia, COVID-19, and febrile neutropenia.
Despite these events, investigators concluded that the overall safety profile remained manageable and aligned with previous clinical experience involving epcoritamab and the accompanying therapies.
Experts Highlight Potential to Change Clinical Practice
Professor Catherine Thieblemont, M.D., Ph.D., Head of the Hemato-Oncology Department at Paris Cité University and Hôpital Saint-Louis Assistance-Publique–Hôpitaux de Paris, emphasized the importance of expanding treatment options for patients living with follicular lymphoma.
She explained that because the disease remains incurable, patients frequently experience repeated relapses throughout their lives.
Each recurrence typically results in progressively shorter periods of remission while reducing the number of available treatment choices.
According to Professor Thieblemont, the results from the EPCORE FL-1 study are clinically meaningful and suggest that the TEPKINLY combination has the potential to alter the treatment paradigm by offering patients a chemotherapy-free regimen capable of producing durable responses earlier during disease relapse.
Genmab Sees Expansion Across B-Cell Malignancies
Judith Klimovsky, M.D., Executive Vice President and Chief Development Officer of Genmab, described the European Commission approval as an important milestone both for patients and for the company’s long-term development strategy.
She noted that providing an effective treatment option during first relapse is particularly valuable because timely intervention may influence long-term disease management.
Klimovsky also emphasized that the approval further establishes TEPKINLY as a foundational therapy across multiple B-cell malignancies.
Beyond its established role as monotherapy in advanced disease, the new indication validates the use of epcoritamab in combination regimens and earlier treatment settings, expanding its potential impact across lymphoma care.
Patient Community Welcomes New Treatment Option
Patient advocacy organizations also welcomed the approval.
Dr. Mitchell Smith, Chief Medical Officer of the Follicular Lymphoma Foundation, noted that living with follicular lymphoma often involves repeated cycles of remission, relapse, and additional treatment.
This recurring pattern creates both physical and emotional challenges for patients and their families.
According to Dr. Smith, the availability of epcoritamab in combination with lenalidomide and rituximab provides an innovative new therapeutic option that offers renewed hope for the follicular lymphoma community across Europe.
Reinforcing the Evolution of Immunotherapy
The approval also reflects broader advances occurring within lymphoma treatment.
Over the past decade, immunotherapies—including monoclonal antibodies, CAR-T cell therapies, antibody-drug conjugates, and bispecific antibodies—have increasingly transformed management of B-cell malignancies.
Bispecific antibodies such as epcoritamab are particularly attractive because they combine targeted cancer recognition with activation of the patient’s immune system without requiring individualized cell manufacturing.
Their availability also expands treatment options for patients who may not be candidates for more complex cellular therapies.
As evidence supporting these therapies continues to accumulate, many experts anticipate that bispecific antibodies will play an increasingly important role across multiple stages of lymphoma treatment.
The European Commission’s approval of TEPKINLY® (epcoritamab) in combination with lenalidomide and rituximab represents a significant advancement for adults living with relapsed or refractory follicular lymphoma. Supported by the robust results of the Phase 3 EPCORE FL-1 trial, the chemotherapy-free regimen demonstrated substantial improvements in progression-free survival, overall response rates, and complete response rates compared with the current standard of care.
Beyond offering patients a new therapeutic option during a critical stage of disease recurrence, the approval further reinforces TEPKINLY’s expanding role across B-cell malignancies and highlights the growing impact of bispecific antibody therapies in modern hematologic oncology. As physicians begin incorporating the regimen into clinical practice throughout Europe, the therapy has the potential to improve long-term disease management while providing patients with a highly effective immunotherapy-based alternative to conventional treatment approaches.
About the EPCORE FL-1 Trial
EPCORE® FL-1 (NCT05409066) is a Phase 3 open-label interventional trial to evaluate the safety and efficacy of epcoritamab plus lenalidomide and rituximab (R2) versus R2 alone in patients with relapsed/refractory (R/R) follicular lymphoma (FL). The Phase 3 EPCORE FL-1 study included patients with relapsed or recurrent FL following at least one prior line of treatment across a broad range of patient characteristics and disease risk factors. Patients were randomized to receive epcoritamab in combination with R2 (n=243) or R2 alone (n=245).
Patients received epcoritamab 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). The pivotal Phase 3 EPCORE FL-1 trial results were published in The Lancet in January 2026.
About Epcoritamab
Epcoritamab 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 the U.S. and Japan, and TEPKINLY® in the European Union) has received regulatory approval in certain lymphoma indications in more than 65 territories. Epcoritamab is being co-developed by Genmab and AbbVie as part of the companies’ oncology collaboration. The companies share commercial responsibilities in the U.S. and Japan, with AbbVie responsible for further global commercialization. Both companies will pursue additional international regulatory approvals for the investigational relapsed or refractory (R/R) follicular lymphoma (FL) indication and additional approvals for the R/R diffuse large B-cell lymphoma (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 several Phase 3, open-label, randomized trials, including a trial evaluating epcoritamab in combination with R-CHOP in adult patients with newly diagnosed DLBCL (NCT05578976).
a trial evaluating epcoritamab in combination with lenalidomide compared to chemotherapy infusion in patients with R/R DLBCL (NCT06508658), and a trial evaluating epcoritamab in combination with lenalidomide and rituximab (R2) compared to chemoimmunotherapy in patients with previously untreated FL (NCT06191744). The safety and efficacy of epcoritamab has not been established for these investigational uses.