New Mechanism of Action for the Treatment of Previously Treated B-Cell Lymphomas

B-cell lymphomas are malignant diseases affecting a specific subgroup of white blood cells, the B lymphocytes. In B-cell lymphomas, these cells undergo malignant transformation, which can lead to the development of various forms of lymphoma, such as diffuse large B-cell lymphoma (DLBCL) or chronic lymphocytic leukemia (CLL). Standard treatment usually involves chemotherapy combined with immunotherapy. Newer forms of therapy aim to more specifically identify and destroy the diseased cells while minimizing damage to healthy cells—something that is often not possible with conventional chemotherapy. A new approach in the treatment of B-cell lymphomas is the inhibition of the enzyme MALT1. Inhibiting MALT1 disrupts the metabolism of B cells, causing the cells to die.

The goal of this study is to investigate a novel drug from this group of MALT1 inhibitors, known as ABBV-525, in order to determine the optimal dose for treatment and to assess its tolerability and efficacy. This will be conducted in three phases (dose-finding, dose optimization, and extended administration): In the first phase, the dose will be increased; based on these data, the dose will then be optimized in the second phase; and in the third phase, the dose established in the second phase will be administered for a longer period. These three dose-finding phases will last approximately 64 months, and patients will undergo regular clinical evaluations to assess the efficacy and safety of the new drug. All patients will receive the drug ABBV-525 in tablet form. Women and men aged 18 and older with DLBCL or CLL who have already received at least three prior lines of therapy are eligible to participate in the study. In the first dose-finding phase, all patients with B-cell lymphomas who meet the study criteria are eligible to participate. In Phase 2, only those with chronic lymphocytic leukemia (CLL), with or without a specific mutation in the BTK enzyme, are eligible. In Phase 3, patients with non-germ center (non-GCB) diffuse large B-cell lymphoma (DLBCL) are eligible if they have already been treated with CAR-T cell therapy or stem cell transplantation, or if they are not eligible for these treatments. There must be no active involvement of the central nervous system.