New bispecific antibody (drug: AZD0486) for relapsed or uncontrolled follicular lymphoma or diffuse large B-cell lymphoma

B-cell non-Hodgkin lymphomas (B-NHL) are a group of cancers of the lymphatic system that originate in B cells, a subgroup of white blood cells. They are part of the immune system and play a role in defending against pathogens, for example. Diffuse large B-cell lymphoma (DLBCL) usually spreads rapidly if left untreated. Follicular lymphoma (FL) is characterized by slow progression. The exact cause is unknown, but risk factors may include a weakened immune system, certain viruses, or genetic mutations. Treatment often involves immunochemotherapy or, more recently, targeted drugs that can identify and destroy the abnormal cells even more effectively. Nevertheless, these treatments can fail (refractory) or the disease can return (recurrence), which is why new therapies are needed.

AZD0486 is a novel, bispecific antibody that can specifically bind to two different structures on the cell surface and thus recognize them. “Bispecific” means that it targets two different surface proteins simultaneously—CD19 on B cells and CD3 on T cells—to activate the immune system specifically against certain blood cancers. AZD0486 links T cells—another type of the body’s own immune cells—to CD19-positive cancer cells (B cells), enabling the T cells to recognize and destroy the tumor cells. Compared to earlier bispecific antibodies, AZD0486 was developed to cause a lower release of pro-inflammatory signaling molecules (cytokines), which can reduce the risk of what is known as cytokine release syndrome (CRS). CRS is a severe immune system reaction that can occur as a side effect of certain immunotherapies. It involves the sudden release of large amounts of inflammatory substances, which can lead to fever, circulatory problems, or even organ failure. It is treatable but must be detected and monitored quickly.

The goal of the SOUNDTRACK-B study is to investigate the optimal dosage and efficacy of the new antibody. The study is divided into two modules: Module 1 includes patients with FL, and Module 2 includes patients with DLBCL. Both groups will receive the study drug, and its efficacy will be evaluated after 12 months. The study is open-label, meaning that both patients and physicians know that AZD0486 is being administered. Overall, regular follow-up care will be provided for up to 5 years after the start of the study.

Eligible participants are men and women between the ages of 18 and 80 with a confirmed diagnosis of FL or DLBCL who have undergone at least two prior treatments. In addition, the tumor cells must express the surface marker CD19. Individuals with other forms of lymphoma, such as chronic lymphocytic leukemia, Burkitt lymphoma, or Richter transformation, as well as those with active involvement of the central nervous system, are excluded from participation. Patients with pre-existing neurological conditions such as epilepsy, stroke, or dementia, as well as those who have recently received certain immunotherapies or stem cell transplants, are also ineligible to participate.