European Commission Approves TEPKINLY + R2 for Relapsed or Refractory Follicular Lymphoma in the Second-Line Setting – Genmab
Genmab A/S announced that the European Commission (EC) granted marketing authorization for Tepkinly (epcoritamab) in combination with lenalidomide and rituximab (Tepkinly + R2) for the treatment of adult patients with relapsed or refractory (R/R) follicular lymphoma (FL). The approval is based on results from the pivotal Phase 3 EPCORE FL-1 trial that evaluated fixed-duration Tepkinly + R2 compared to standard of care R2.
Tepkinly (epcoritamab) plus lenalidomide and rituximab (R2) is the first and only bispecific-based therapy approved in Europe for the treatment of follicular lymphoma in the second-line setting, offering a chemotherapy-free option
In the Phase 3 EPCORE FL-1 trial, fixed-duration Tepkinly + R2 demonstrated significantly superior progression-free survival and overall response rates compared to R2, with approximately three out of four patients achieving a complete response
“Follicular lymphoma is a persistent form of cancer that remains incurable, which means patients need more treatment options. Patients often relapse and experience shorter remissions and have fewer treatment options each time the disease returns. The results shown in the EPCORE FL-1 trial are clinically meaningful, demonstrating the potential for Tepkinly + R2 to change the treatment paradigm for patients, offering the chance at a durable response with a chemotherapy-free option.” – Catherine Thieblemont, M.D., Ph.D., head of the hemato-oncology department, Paris Cité University, Hôpital Saint-Louis Assistance-Publique-Hopitaux de Paris (APHP) in Paris.
The marketing authorization is supported by data from the Phase 3 EPCORE FL-1 trial, an open-label interventional trial to evaluate the safety and efficacy of Tepkinly + R2 compared to R2 alone in patients with R/R FL. The study demonstrated Tepkinly + 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 R2 alone. The overall response rate (ORR) in patients treated with Tepkinly + R2 was 96% (95% CI: 90.2, 98.6) compared to 81% in patients treated with R2 (95% CI: 72.7, 87.7; p<.0001). Among patients who were treated with Tepkinly + R2, 74% achieved a complete response (CR) (n=181/243, 95% CI: 68.5, 79.8) compared to a 43% CR rate among patients treated with R2 (n=106/245, 95% CI: 37.0, 49.7).
The safety profile of Tepkinly + R2 in the EPCORE FL-1 study was consistent with the known safety profiles of the individual regimens (epcoritamab and R2). In the trial, the most common (≥ 20%) adverse reactions were neutropenia, rash, upper respiratory tract infections, fatigue, diarrhea, injection site reactions, anemia, constipation, thrombocytopenia, cytokine release syndrome (CRS), hypogammaglobulinemia, COVID-19, pyrexia, and pneumonia. Serious adverse reactions occurred in 44% of patients who received epcoritamab in combination with lenalidomide and rituximab. Serious adverse reactions in ≥ 5% of patients included CRS, pneumonia, COVID-19, and febrile neutropenia.
“The marketing authorization of Tepkinly + R2 by the European Commission represents a pivotal moment for individuals living with follicular lymphoma, providing a treatment option at first relapse, when effective intervention is critical. This milestone reinforces Tepkinly’s potential as a core therapy across B-cell malignancies, validating its use in combination and earlier follicular lymphoma settings, while building upon its established efficacy as a monotherapy in advanced disease.” – Judith Klimovsky, M.D., Executive Vice President & Chief Development Officer of Genmab.
FL is typically a slow-growing form of non-Hodgkin lymphoma (NHL) that arises from B-cell lymphocytes. FL is the second most common form of NHL overall, accounting for 20-30 percent of all NHL cases.i FL incidence is significantly higher in European populations, 11-29 percent, compared to non-European populations, 2-18 percent.ii FL is considered incurable, and there is no standard of care treatment for third-line or later FL.i,iii Patients who achieve remission also often experience relapse.
“A diagnosis of follicular lymphoma can bring a relentless cycle of disease recurrence and treatment. The approval of epcoritamab now in combination with R2 in Europe is a welcome advance that will bring an innovative treatment option and hope to the follicular lymphoma community.” – Mitchell Smith, M.D., Ph.D., Chief Medical Officer of the Follicular Lymphoma Foundation.
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.
