New bispecific antibody (mosunetuzumab) for the treatment of chronic lymphocytic leukemia (CLL)

Chronic lymphocytic leukemia (CLL) is a malignant disease of the hematopoietic system in which the bone marrow produces an uncontrolled number of B lymphocytes and releases them into the blood. Lymphocytes are a subtype of white blood cells that are part of the immune system. If the lymphocytes are instead found primarily in the lymph nodes and the spleen, the condition is referred to as small-cell lymphocytic lymphoma (SLL), which is grouped together with CLL as a single disease. CLL is a type of non-Hodgkin lymphoma and typically progresses slowly. It occurs primarily in older adults. The causes of CLL are not yet fully understood, but genetic factors (acquired mutations) play a role.

Treatment depends on the severity of symptoms and usually begins only when symptoms appear. The treatment depends on several factors, including specific characteristics of the affected cancer cells. In addition to immunochemotherapy, targeted therapies are also used (e.g., with a BTK inhibitor such as ibrutinib). Another active ingredient, which is also used in combination therapy, is venetoclax. If the disease flares up again (relapse) or becomes uncontrollable (refractory), the treatment strategy must be changed. New drugs are constantly being sought for this situation.

The goal of this Phase 1b study is to investigate the safety, efficacy, and pharmacokinetics of mosunetuzumab. Mosunetuzumab is a specific bispecific antibody that binds simultaneously to cancer cells (via CD20) and immune cells (T cells via CD3), thereby helping the immune system recognize and destroy the cancer cells. The drug is already approved for the treatment of relapsed/refractory follicular lymphoma, another type of lymphoma. The active ingredient is administered subcutaneously (under the skin).

As part of the study, patients will receive either mosunetuzumab as monotherapy or in combination with venetoclax. Which regimen is used depends on whether treatment with a BTK inhibitor has already been completed or is currently underway. Based on this, the study has a total of 3 arms (cohorts). In addition, tocilizumab is administered, a medication that can curb excessive immune responses. The study is open-label, meaning that both the medical staff and the patient know which medications are being administered. The study will run for up to 24 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 treatment. The primary endpoint of the study is the occurrence of dose-limiting side effects (safety and tolerability).

Patients aged 18 and older with CLL are eligible to participate in this study. Patients must have received at least two prior lines of therapy (including a BTK inhibitor and/or venetoclax) and must be either refractory or have experienced a relapse. In addition, patients who are currently experiencing disease progression while on BTK inhibitor therapy may receive monotherapy with mosunetuzumab (Arm B).