ABBV-453 (a new BCL-2 inhibitor) combined with obinutuzumab for relapsed/refractory CLL/SLL

Chronic lymphocytic leukemia (CLL) is a disease affecting a specific subtype of white blood cells (lymphocytes). CLL is the most common form of leukemia in Western countries. Small lymphocytic lymphoma (SLL) is closely related, so the two conditions are often grouped together. The disease can affect people of various age groups, although the median age of onset is 70 years.

Treatment for CLL/SLL is usually not initiated until patients show symptoms of the disease. Prior to that, CLL may be monitored so that intervention can occur if the condition worsens. The choice of medication depends on the patient’s overall health, other relevant medical conditions, and genetic alterations in the CLL cells. Treatment approaches have evolved. Instead of the former standard of immunochemotherapy, targeted inhibitors of specific structures on or within the cells are now frequently used. This causes the malignant cells to die in a targeted manner; fortunately, side effects on other cells are usually minimal. This has significantly improved the prognosis for patients. Furthermore, there is a great deal of research into new medications, especially for situations where the disease either returns or cannot be controlled with existing medications (recurrence/refractory).  ABBV-453 is a new, not-yet-approved drug that is currently being evaluated in various clinical trials. It targets a specific mechanism (BCL-2) in the cancer cell that causes the cell to die (similar to the already established Venetoclax).

The goal of this study is to investigate whether patients who have experienced relapses or disease progression during at least two previous lines of treatment can benefit from a combination therapy consisting of the established drug obinutuzumab (antibody) and the new experimental drug ABBV-453. Obinutuzumab is used at the start to reduce the tumor burden before treatment with ABBV-453. All patients participating in the study will receive the experimental treatment and will be assigned to five consecutive groups to determine the appropriate dose (dose escalation). Accordingly, 5 dose levels will be tested, with each patient assigned to one level and remaining in that level throughout the study. In the second part of the study (dose expansion), patients will then receive the determined dose of ABBV-453 in combination with obinutuzumab or, in the second study arm, ABBV-453 alone without obinutuzumab. Treatment and follow-up will continue for approximately 5 years.

Women and men aged 18 and older with chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL) who have already received at least two lines of standard therapy and have experienced a relapse or progression of the disease during that treatment are eligible to participate in the study. There must be no treatment option that the treating physicians consider more suitable. No treatment with a BCL-2 inhibitor may have been administered within 6 months prior to the start of study therapy. Certain comorbidities may be grounds for exclusion from the study.