New bispecific antibody (epcoritamab) for the treatment of chronic lymphocytic leukemia, including Richter syndrome

Chronic lymphocytic leukemia (CLL) is a type of cancer in which the bone marrow produces large quantities of abnormal B lymphocytes and releases them into the bloodstream. Lymphocytes are a type of white blood cell that is part of the body’s immune system. If the lymphocytes are found primarily in the lymph nodes and the spleen, the condition is referred to as small-cell lymphocytic lymphoma (SLL). These conditions are very similar and are often grouped together as a single disease. CLL is a type of non-Hodgkin lymphoma (NHL); it usually occurs later in life, and it often takes a long time before treatment becomes necessary. Certain risk factors play a key role in this. “High-risk” CLL can also grow rapidly and aggressively. Richter’s syndrome (RS) is a rare complication of CLL. In this condition, highly malignant cancer cells develop. This leads to rapid enlargement of the lymph nodes and the development of symptoms such as anemia, fever, or weight loss. Treatment depends on the severity of the symptoms and the patient’s overall physical condition. Immunochemotherapy is typically used.

If the disease recurs or becomes uncontrollable (refractory), the treatment must be changed. Epcoritamab is already approved for other forms of NHL; it is a so-called bispecific antibody that can both bind to cancer cells and stimulate the body’s own immune system.

The goal of the EPCORE™ CLL-1 study is to investigate this drug in patients with CLL/SLL or Richter syndrome. The study consists of two phases: The goal of Phase 1 is to determine the optimal dosage of the study drug. In addition to monotherapy with epcoritamab, the drug will also be administered in combination with the approved medications venetoclax, lenalidomide, pirtobrutinib, or R-CHOP, an established immunochemotherapy regimen. The exact treatment plan depends on the specific clinical situation or is assigned by the study team. The study is open-label, meaning that both the medical staff and the patient know which medications are being administered. Following Phase 1, treatment will be administered in several cycles (Phase 2). Treatment as part of the study will continue for up to 60 months, during which the efficacy of the therapy and the occurrence of side effects from the various medications will be evaluated. The key factor is whether or when the disease progresses again during therapy.

Patients aged 18 and older with treatment-resistant (refractory) or relapsed CLL or SLL, as well as patients aged 18 and older with RS, are eligible to participate in the study. If a patient has “high-risk” CLL, they may participate in the study immediately without prior treatment.