New Drug Candidate (ABBV-101) for the Treatment of Previously Treated B-Cell Lymphomas

B-cell lymphomas originate from a specific subgroup of white blood cells called B lymphocytes. In B-cell lymphomas, these cells undergo malignant transformation, which can lead to the development of various forms of lymphoma. The most common B-cell lymphomas are diffuse large B-cell lymphoma (DLBCL), follicular lymphoma (FL), mantle cell lymphoma (MCL), chronic lymphocytic leukemia (CLL), including small lymphocytic lymphoma (SLL). This study is generally aimed at patients with B-cell lymphoma. Standard treatment usually involves chemotherapy combined with immunotherapy. Newer forms of therapy aim to more specifically identify and destroy the diseased cells while causing as little damage as possible to healthy cells—something that is often not possible with conventional chemotherapy. One such target, which has been the focus of drug development for several years and plays an important role in the malignant transformation of B cells, is the enzyme Bruton’s tyrosine kinase (BTK). So-called BTK inhibitors (e.g., ibrutinib) are already approved and are an integral part of standard therapy for various B-cell lymphomas. A new therapeutic approach involves not only inhibiting this enzyme but also degrading (= destroying) it. This corresponds to the mechanism of action of the new drug (ABBV-101).

The goal of this Phase 1/2 study is to investigate ABBV-101 in clinical use. The drug specifically targets BTK and degrades this enzyme. The study is divided into two phases. In the first phase (dose escalation), the drug is administered in increasing doses to determine the maximum tolerated dose (MTD). In the second phase (dose expansion), this determined dose will be administered to additional patients, and data on the drug’s efficacy and safety will be collected. The study is scheduled to last approximately 2 years, with a maximum duration of 5 years. The study is single-arm, meaning that all patients will receive the new drug ABBV-101.

Women and men aged 18 and older who have B-cell lymphoma and have already undergone three or more lines of treatment are eligible to participate in the study. Conditions that qualify for participation include: chronic lymphocytic leukemia (CLL), small lymphocytic lymphoma (SLL), diffuse large B-cell lymphoma (DLBCL) that is relapsed or refractory following CAR-T cell therapy or hematopoietic cell transplantation (HCT), as well as DLBCL of the following subtypes: DLBCL not otherwise specified (NOS) of the germinal center B-cell (GCB) and non-GCB types, T-cell/histiocyte-rich large B-cell lymphoma, primary mediastinal (thymic) large B-cell lymphoma, intravascular large B-cell lymphoma, ALK-positive large B-cell lymphoma, highly malignant B-cell lymphoma with MYC and BCL2 and/or BCL6 rearrangements, and highly malignant B-cell lymphoma, unspecified (NOS). Other diseases include mantle cell lymphoma (MCL), follicular lymphoma (FL, grades 1–3b), marginal zone lymphoma (MZL; splenic, extranodal, and nodal), Waldenström macroglobulinemia (WM), and transformed indolent non-Hodgkin lymphomas (iNHL). There must be no acute involvement of the central nervous system.