Study of Subcutaneous Epcoritamab in Combination With Intravenous Rituximab and Oral Lenalidomide (R2) to Assess Adverse Events and Changes in Disease Activity in Adult Participants With Follicular Lymphoma

Follicular lymphoma (FL) is a form 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 body’s 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 patient’s symptoms and overall physical condition. Patients with early-stage (limited) FL usually receive radiation therapy. Standard treatment for advanced-stage FL often involves a combination of chemotherapy and immunotherapy. In cases of recurrence or a treatment-resistant form of FL, one treatment option is the combination of lenalidomide and rituximab. In this approach, cancer cells are recognized and attacked by the immune system through this modification.

Epcoritamab is a so-called bispecific antibody that can both bind to cancer cells and stimulate the body’s own immune system. This drug is already approved for use in another form of NHL when standard therapy has failed.

The goal of this Phase 3 study is to investigate the efficacy and safety of epcoritamab in combination with rituximab and lenalidomide in a larger number of patients with FL and to compare it with the current standard of care—lenalidomide plus rituximab. Participants will be randomly assigned to 3 groups. Group 1 will receive the combination of lenalidomide with rituximab + epcoritamab at dose A, Group 2 will receive the combination of lenalidomide with rituximab + epcoritamab at dose B, and Group 3 will receive only the combination of lenalidomide with rituximab (control group). Enrollment in Group 2 has already been completed, so new patients will be assigned to Group 1 or 3. Treatment in each group consists of 12 cycles, each lasting 28 days. Rituximab is administered via an intravenous line, lenalidomide is taken in capsule form, and epcoritamab is injected subcutaneously. The study is open-label, meaning that both the doctor and the patient know which medication is being administered. Treatment as part of the study lasts for up to 60 months, during which the efficacy of the therapy and the occurrence of side effects from the various medications are evaluated. The key factor is whether or when the disease progresses again during treatment.

Patients aged 18 and older who have uncontrollable (refractory) FL or FL with disease progression (recurrence) are eligible to participate in this study. They must not have previously received lenalidomide (within the last 12 months).