A new drug (designated BMS-986458), either alone or in combination with rituximab, for the treatment of relapsed or refractory follicular lymphoma or diffuse large B-cell lymphoma following at least two prior lines of therapy

Non-Hodgkin lymphomas (NHL) originate from a specific subgroup of white blood cells called B lymphocytes. NHL is an umbrella term for various diseases in which B-cell lymphocytes undergo malignant transformation, leading to the development of different forms of lymphoma. Common B-cell lymphomas include diffuse large B-cell lymphoma (DLBCL) and follicular lymphoma (FL), with DLBCL itself having several subtypes. Standard treatment usually involves chemotherapy combined with immunotherapy, primarily the antibody rituximab. Newer forms of therapy aim to identify and destroy the diseased cells more precisely while minimizing damage to healthy cells—something that is often not fully possible with conventional chemotherapy. To achieve this, researchers look for specific markers on the cell surface or inside the lymphoma cells and develop corresponding drugs. A new drug called BMS-986458 is a so-called ligand-directed degrader (LDD) that specifically degrades the BCL6 protein. BCL6 is a factor in the proliferation of cancer cells that plays a key role in various B-cell lymphomas, such as diffuse large B-cell lymphoma (DLBCL) and follicular lymphoma (FL). The degradation of BCL6 impairs the survival and growth of cancer cells.

The goal of this study is to administer the drug BMS-986458 to patients with DLBCL or FL to investigate the optimal dose and safety (Phase 1) and efficacy (Phase 2). All study participants will receive the drug BMS-986458. They will be randomly assigned to one of two groups. One group will receive BMS-986458 alone (monotherapy), while the other will receive BMS-986458 in combination with the antibody rituximab. Patients will be treated as part of the study for a period of approximately 2 years.

Women and men aged 18 and older who have DLBCL or FL and have already received at least two lines of treatment are eligible to participate in the study. Prior to the start of treatment, they may have received radiation therapy, CAR-T cell therapy, or a stem cell transplant, provided that a certain amount of time has elapsed since the study began. The brain must not be affected by the disease.