BGB-16673 (BTK inhibitor) in combination with other active ingredients for the treatment of relapsed/refractory B-cell disorders

B-cell malignancies are malignant diseases of the immune system that originate in so-called B cells—white blood cells responsible for producing antibodies. These diseases primarily manifest as lymphomas (cancer of the lymph nodes) or leukemias (blood cancer). Depending on the type of disease, its stage, and the patient’s overall health, various treatments are used. Standard treatment usually consists of a combination of chemotherapy, immunotherapies, targeted therapies, and, in some cases, stem cell transplantation. If the disease continues to progress or recurs despite previous treatments, it is referred to as refractory or recurrent cancer. In these cases, treatment options are often limited.BGB-16673 is a novel active ingredient (a Bruton’s tyrosine kinase-targeted protein degrader) that was specifically developed for the treatment of certain B-cell disorders in which conventional therapies are no longer sufficient. It is a drug that specifically targets the enzyme Bruton’s tyrosine kinase (BTK), which plays a key role in the survival and growth of B-cell cancer cells. Conventional BTK inhibitors (such as ibrutinib or zanubrutinib) inhibit this enzyme—but sometimes the cancer cells develop resistance to them. BGB-16673 works differently: Instead of merely blocking BTK, it completely degrades the enzyme within the cell. This allows it to target even those cancer cells that have previously become resistant to BTK inhibitors.

The goal of the study is to investigate the safety and efficacy of the drug BGB-16673 in combination with other active substances—Sonrotoclax, Zanubrutinib, Mosunetuzumab, or Glofitamab (substudies 1–4). Assignment to one of the substudies depends on the individual course of the disease, such as whether the patient has already received certain prior treatments (e.g., BTK inhibitors), or whether certain biological characteristics (such as CD20 expression) are present. This is therefore a non-randomized study: Doctors decide, based on medical criteria, which combination therapy is appropriate for a patient. The study is divided into several phases. First, in Phase 1, researchers test which drug combinations and dosages are well tolerated (dose-finding). Phase 2 then evaluates the treatment’s efficacy. The medications are administered as tablets or via infusion. The duration of treatment is individualized, depends on the patient’s response to therapy, and may last several months. Follow-up monitoring continues for up to 3 years after the last dose to assess side effects and long-term effects.

Eligible participants include women and men aged 18 and older with a previously treated B-cell disease that is progressing despite therapy (refractory) or has recurred (relapse). Excluded are, among others, patients with untreated brain metastases, active infections, recent stem cell or CAR-T cell therapy (within 3 months), or a history of severe allergic reactions to the study medications. Other active cancers or certain prior treatments may also lead to exclusion.