Epcoritamab (a new bispecific antibody) in combination with rituximab and lenalidomide as first-line therapy for follicular lymphoma

Follicular lymphoma (FL) is a type of non-Hodgkin lymphoma (NHL) in which malignant B lymphocytes accumulate in the lymph nodes. Lymphocytes are a type of white blood cell that is part of the immune system. The cause of FL is not fully understood, but genetic mutations and immune system disorders play a role. This disease is chronic and generally incurable with available standard therapies, but it can often be effectively controlled for a long time. Treatment is tailored to the symptoms and physical condition of the affected patients. Patients with early-stage (limited) FL usually receive radiation therapy. The standard treatment for advanced-stage FL involves a combination of chemotherapy and immunotherapy. In cases of relapse or a refractory form of FL, one treatment option is the combination of lenalidomide with rituximab (R²). The combination of the investigational drug epcoritamab with R² could represent another treatment option for follicular lymphoma. Epcoritamab is a bispecific antibody that targets cancer cells while simultaneously stimulating the immune system; it is already approved for the treatment of relapsed/refractory diffuse large B-cell lymphoma (DLBCL).

The EPCORE™FL-2 study (Phase 3 trial) is investigating the efficacy and safety of epcoritamab in combination with R² compared to various standard therapies. Patients are randomly assigned to five groups as part of the study. This study is examining five different treatment groups to determine which therapy is the most effective and best tolerated for previously untreated follicular lymphoma. One group receives the new combination of epcoritamab, rituximab, and lenalidomide—which is designed to strongly activate the immune system against cancer cells. Two other groups receive established standard therapies with chemotherapy: either rituximab or obinutuzumab combined with CHOP or bendamustine. Another group receives only rituximab and lenalidomide without epcoritamab—a standard chemotherapy-free treatment. The final group receives a personalized standard therapy selected by the physician, depending on what is most suitable for the patient. The goal is to directly compare the different treatment approaches to identify the best treatment option for patients with this disease. The study is open-label, meaning that both the medical staff and the patient know which medications are being administered. Treatment lasts 120 weeks, and follow-up examinations as part of the study will continue for up to 10 years, during which the effectiveness of the therapy and the occurrence of side effects from the various medications will be evaluated. The key factors are whether the disease responds completely to the therapy and how long the disease-free survival rate is after treatment.

Men and women aged 18 and older with untreated stage 2–4 follicular lymphoma are eligible to participate in this study.