New treatment approach (drug: BGB-16673) as an adjunct to standard therapy with BTK inhibitors for various B-cell lymphomas

B-cell non-Hodgkin lymphomas (NHL) are malignant diseases of the lymphatic system that affect B lymphocytes, a subtype of white blood cells that are part of the immune system. NHL is an umbrella term for a group of diseases that have different characteristics but originate from the same malignant cells. These include, among others: marginal zone lymphoma (MZL), follicular lymphoma (FL), mantle cell lymphoma (MCL), chronic lymphocytic leukemia (CLL), small lymphocytic lymphoma (SLL), Waldenström macroglobulinemia (WM), and diffuse large B-cell lymphoma (DLBCL). Richter’s syndrome (RS) describes the transformation of CLL into an aggressive lymphoma (usually DLBCL). The most common symptoms include swollen lymph nodes, an enlarged spleen, fatigue, exhaustion, fever, night sweats, and weight loss. Treatment depends, among other factors, on the type of disease, the patient’s age, and their overall physical condition. Currently, the standard treatment for NHL includes immunochemotherapy or therapy with drugs that inhibit specific structures in the malignant cells. This includes, for example, treatment with a Bruton’s tyrosine kinase inhibitor (BTK inhibitor), which specifically inhibits cell growth and thus causes the cells to die. These therapies are usually very effective; however, the disease may recur, or the disease may not respond to treatment (refractory).

A new therapeutic approach, which also targets Bruton’s tyrosine kinase (BTK), does not inhibit it—as BTK inhibitors do—but instead directly destroys BTK (BTK degrader) and thus the effect of BTK in the malignant cells, causing them to die.

The goal of the CaDAnCe-101 study is to investigate the safety, efficacy, and optimal dose of BGB-16673, a novel drug that degrades BTK. This is a Phase 1/2 study. In Phase 1 of the study (dose escalation), the dose is gradually increased. During this phase, patients are closely monitored, and the occurrence of side effects is assessed. The optimal drug dose for further treatment is then determined. In Phase 2 (dose expansion), this dose will be tested in a larger group of patients, with patients assigned to a cohort based on their NHL subtype. The study is open-label, meaning that both the medical staff and the patient know which medication is being administered. Treatment and follow-up visits as part of the study will continue for up to 3 years, during which the efficacy of the therapy and the occurrence of side effects at various drug doses will be evaluated. A key factor is whether or when the disease progresses again during treatment. In Phase 2 of the study, the primary focus is on efficacy as measured by the overall response rate.

Patients aged 18 and older with the B-cell disorders listed above are eligible to participate in this study. For some of the cohorts within the study, prior treatment with a BTK inhibitor is a prerequisite. There must be no involvement of the central nervous system.