Can a new drug enhance the effectiveness of rituximab—a standard treatment for non-Hodgkin lymphoma—if the disease becomes active again?

Indolent B-cell non-Hodgkin lymphomas (NHL) are a group of slow-growing lymphomas that originate in B cells, a type of white blood cell. These lymphomas can take various forms, including follicular lymphoma (FL), mantle cell lymphoma (MCL), and marginal zone lymphoma (MZL). “Indolent” means that they often do not cause immediate symptoms and progress only slowly; this is in contrast to aggressive NHLs, which can cause significant symptoms within a short period of time. However, this does not mean that these lymphomas are harmless; treatment is usually necessary as the disease progresses. Typical symptoms include swollen lymph nodes, fatigue, and infections. Standard treatment often includes rituximab, an antibody that binds to a protein (CD20) on B cells and destroys them. However, some patients do not respond adequately to treatment or experience a relapse. BMS-986458 is a novel drug currently in clinical development for the treatment of certain B-cell lymphomas. BMS-986458 is a so-called ligand-directed degrader (LDD) that specifically degrades the BCL6 protein. The degradation of BCL6 impairs the survival and growth of cancer cells.

The goal of the 17-BI-1206-02 study (Phase 1/2 trial) is to investigate the tolerability and efficacy of the new antibody BI-1206 in combination with rituximab. The combination of BI-1206 with rituximab is expected to improve the treatment of more resistant lymphomas. The study design consists of two phases. In Phase 1, different doses of BI-1206 in combination with rituximab will be tested to determine the maximum tolerated dose (MTD) and the recommended dose for the subsequent phase. To this end, patients are intentionally (non-randomized) divided into two groups and receive the drug combination either as an intravenous infusion (Group 1) or as a subcutaneous injection (Group 2). All patients are aware of their treatment (open-label). In the second phase, the efficacy of these dosages will be further investigated. Patients remain in their respective groups and initially receive a single dose of the therapy. An evaluation takes place after 6 weeks. Patients who benefit from the treatment continue it for up to one year or until they have completed 6 treatment cycles. Generally, patients receive BI-1206 every 4 weeks; rituximab is administered every 8 weeks. Another group in Phase 2 will additionally receive the drug acalabrutinib, an already approved BTK inhibitor with an established mechanism of action.

Eligible participants include adult men and women with a confirmed diagnosis of follicular lymphoma, mantle cell lymphoma, or marginal zone lymphoma. The disease must have been treated at least once with a rituximab-containing regimen and must have recurred or failed to respond to that treatment. No stem cell transplant may have been performed in the preceding 12 months, and participants must not have any other cancer.