New combination therapies with Sonrotoclax compared with standard therapy for relapsed or refractory CLL/SLL

Chronic lymphocytic leukemia (CLL) and small lymphocytic lymphoma (SLL) are closely related diseases in which B lymphocytes—a subgroup of white blood cells—proliferate uncontrollably. In CLL, the blood and bone marrow are primarily affected, while in SLL, it is mainly the lymph nodes. Both diseases are more common in older adults. Treatment is usually not started until symptoms appear, such as fatigue, frequent infections, or swollen lymph nodes. If the disease returns after treatment, it is referred to as a recurrence. If it does not respond adequately to therapy, it is described as refractory. New treatment options are being investigated for this situation. Treatment has changed fundamentally in recent years. Instead of chemotherapy, targeted drugs are now primarily used. These include BCL-2 inhibitors such as venetoclax, which trigger the natural death of cancer cells, as well as anti-CD20 antibodies such as rituximab and obinutuzumab, which recognize a specific marker (CD20) on the surface of cancer cells and destroy them. Sonrotoclax is a novel BCL-2 inhibitor taken as a tablet. It was developed to bind more strongly and more specifically to the BCL-2 protein in cancer cells than venetoclax and to remain effective even in the presence of certain resistance mechanisms.

The goal of the Phase 3 trial is to determine whether sonrotoclax plus obinutuzumab can prolong the time until disease progression (progression-free survival) compared to standard therapy. To this end, patients will be randomly assigned in a 2:2:1:2 ratio to one of four treatment arms. Sonrotoclax plus obinutuzumab, sonrotoclax plus rituximab, sonrotoclax plus obinutuzumab with a treatment duration adjusted for minimal residual disease (MRD), or the current standard of care, venetoclax plus rituximab. Treatment is administered in 28-day cycles, up to a total of 25 cycles. In the MRD-guided arm, patients initially receive 14 cycles. If no residual disease is detectable afterward, treatment may be discontinued; otherwise, it will continue until a total of 25 cycles have been completed. The study is open-label, meaning that both patients and study physicians know which treatment is being administered. Additional objectives include evaluating response rates, overall survival, and quality of life.

Eligible participants are patients aged 18 and older with a confirmed diagnosis of CLL or SLL who have already received at least one prior treatment for the disease and are in sufficient general health.