Comparison of BGB-16673 with the drug pirtobrutinib in adults with relapsed or refractory chronic lymphocytic leukemia or small-cell lymphocytic lymphoma

Chronic lymphocytic leukemia (CLL) and small lymphocytic lymphoma (SLL) are cancers of the lymphatic system. This system includes, for example, the lymph nodes, spleen, and bone marrow. CLL and SLL are essentially the same disease, in which mature white blood cells (B lymphocytes) multiply uncontrollably. The difference is that CLL also spreads into the blood. The disease often progresses very slowly, and in many cases, it is initially monitored without treatment. If the cancer cells begin to displace healthy bone marrow, for example, treatment becomes necessary. A key protein that drives the growth of these cancer cells is Bruton’s tyrosine kinase (BTK). Standard therapy often involves the use of so-called covalent BTK inhibitors, which permanently block this protein. Over time, however, the cancer cells can develop resistance, rendering these drugs ineffective. In such cases, other mechanisms of action are often employed, such as non-covalent BTK inhibitors (e.g., pirtobrutinib). This study investigates the new drug candidate BGB-16673. It is a so-called “BTK-targeted protein degrader.” Instead of merely blocking the BTK protein, this compound aims to have the protein broken down by the cell’s own disposal system. This mechanism will be evaluated to determine whether it is more effective and better tolerated than treatment with pirtobrutinib. BGB-16673 has not yet been approved for treatment.

The goal of this Phase 3 study is to directly compare BGB-16673 with pirtobrutinib. Patients will be randomly assigned to two groups. Group A will receive the study drug BGB-16673, while Group B will receive the comparator drug pirtobrutinib. Both drugs are taken as tablets. The study is open-label, which means that both patients and medical staff know which drug is being administered. The primary endpoint of the study is progression-free survival (PFS) over 3 years—that is, the length of time during which the disease does not progress.

Adults aged 18 and older who have CLL or SLL and have already been treated with a covalent BTK inhibitor are eligible to participate in the study. The disease must require treatment and must either no longer respond to prior therapy (refractory) or must have returned (recurred). Patients who have already been treated with pirtobrutinib or other non-covalent BTK inhibitors or BTK degraders are excluded from participation. Also excluded are patients with a Richter transformation (conversion to a more aggressive form of lymphoma) or a history of severe blood clotting disorders, strokes, or cerebral hemorrhages.