New Drug (Nemtabrutinib) for the Treatment of Various B-Cell Non-Hodgkin 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, although caused by the same abnormal cells, have different characteristics. These include, among others: marginal zone lymphoma (MZL), follicular lymphoma (FL), mantle cell lymphoma (MCL), chronic lymphocytic leukemia (CLL), small lymphocytic lymphoma (SLL), and Waldenström macroglobulinemia (WM). Richter’s syndrome (RS) describes the transformation of CLL into a significantly more aggressive lymphoma. 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 specifically inhibit structures within the malignant cells. This includes, for example, treatment with a Bruton’s tyrosine kinase (BTK) inhibitor, which specifically inhibits cell growth and thereby causes the cells to die.

This Phase 1/2 study is investigating the safety, efficacy, and the safest and most effective dose of nemtabrutinib (MK-1026). Nemtabrutinib is a novel BTK inhibitor. The drug has not yet been approved for treatment. In Phase 1a of the study, the dose is gradually increased. During this phase, patients are closely monitored, and the occurrence of side effects is assessed. In Phases 1b and 1c, additional patients will receive the drug according to this protocol, and an optimal dose will be determined for further treatment (Phase 1 has already been completed). In Phase 2, this dose will be evaluated in a larger group of patients (divided into 8 cohorts based on disease and prior treatment). The study is open-label, meaning that both the medical staff and the patient know which drug is being administered. Treatment and follow-up visits as part of the study will continue for up to 5 years, during which the efficacy of the therapy and the occurrence of side effects associated with the various drug doses will be evaluated. The key factor is whether or when the disease progresses again during therapy (maximum 6 years of observation). In Phase 2 of the study, the primary focus is on efficacy as measured by the overall response rate.

Adult patients aged 18 and older with a confirmed diagnosis of certain B-cell lymphomas are eligible to participate in the study. These include, among others, chronic lymphocytic leukemia (CLL), small lymphocytic lymphoma (SLL), mantle cell lymphoma (MCL), follicular lymphoma (FL), marginal zone lymphoma (MZL), Waldenström macroglobulinemia (WM), and Richter syndrome. All patients must have previously received at least one systemic therapy and must now show signs of disease activity again. For certain groups, such as patients with FL, MZL, or WM, at least two prior therapies are required for eligibility. Additionally, there must be no symptoms or active spread of the disease in the central nervous system (CNS)—patients with CNS involvement are excluded. Previous treatment with nemtabrutinib or similar active ingredients, known allergies to components of the medication, active infections (including HIV or hepatitis B/C), and severe cardiovascular diseases also preclude participation.