Epcoritamab, a new bispecific antibody used in combination with various medications to treat patients with non-Hodgkin lymphoma

Non-Hodgkin lymphomas (NHL) refer to a group of lymphomas that includes both aggressive and slow-growing forms, each of which requires highly individualized treatment. These cancers develop when lymphocytes (a type of white blood cell) grow uncontrollably and spread throughout the body. Standard treatments for NHL include chemotherapy, radiation therapy, and immunotherapy. Epcoritamab is an antibody that binds simultaneously to two target molecules (CD20 on the cancer cell and CD3 on T cells) (bispecific) to activate the immune system and destroy the cancer cells.

The goal of the M22-132 study is to investigate the safety and efficacy of epcoritamab in patients with non-Hodgkin lymphoma.

The study has several treatment arms (8 in total) in which epcoritamab is administered in combination with other, already established medications such as lenalidomide, ibrutinib, polatuzumab vedotin, rituximab, cyclophosphamide, doxorubicin, prednisone, and pirtobrutinib. In one arm of the study, the active ingredient “CC-99282” is used as a combination partner; this is a so-called Cereblon E3 ligase modulator (CELMoD), which also targets specific sites in the cancer cell and has not yet been approved. Assignment to groups is based on diagnosis and is also decisive for the selection of therapy. Both the patient and the physician are aware of the assignment (open-label), which is not random. The study design comprises a Phase 1b/2 trial, in which the appropriate dose is first determined based on tolerability and side effects (Phase 1b), and in the second phase, the efficacy of epcoritamab in combination with various medications is tested (Phase 2). Patients receive the medications in cycles of 21 or 28 days, depending on the specific treatment arm. Treatment continues until the disease progresses, intolerable side effects occur, or patients withdraw from the study. Overall, patients will be monitored regularly for up to 5 years after the start of the study.

Eligible participants include adult women and men with a confirmed diagnosis of one of the following non-Hodgkin lymphomas and at least one detectable manifestation of the lymphoma (e.g., affected lymph node). The diagnoses being studied include diffuse large B-cell lymphoma (DLBCL), follicular lymphoma (FL), and mantle cell lymphoma (MCL). In addition, the tumor cells must express the surface marker CD20 on their cell surface (CD20-positive) so that epcoritamab can bind to them.