A new bispecific antibody (designation: AZD0486) for relapsed/refractory B-ALL

Acute lymphoblastic B-cell leukemia (B-ALL) is a malignant disease of the hematopoietic system characterized by the uncontrolled production of malignant blood cells (blasts) in the bone marrow and blood. Blasts are a precursor form of white blood cells, which are part of the immune system. The overproduction of blasts disrupts normal blood formation and immune defense, especially since they are produced in very large, life-threatening quantities. Symptoms often include fatigue, anemia, blood clotting disorders, fever, and an increased susceptibility to infections. The cause of ALL is a genetic abnormality in the blood cells that develops over the course of a person’s life (it is not inherited!). During cell division—which occurs constantly in blood cells as part of the regeneration process in the bone marrow—defective blood cells are then produced. These genetic abnormalities can usually be easily detected. The disease’s risk profile is determined through various tests.

The standard treatment for ALL is divided into several phases: pre-treatment, induction, consolidation, and maintenance therapy. The goal is to eliminate the abnormal cells. In some cases, a stem cell transplant is also used for this purpose. Nevertheless, some patients experience persistent or recurrent disease activity. AZD0486 is a so-called bispecific T-cell engager (BiTE) that aims to trigger the patient’s immune system to specifically attack cancer cells. It simultaneously binds to CD19, a protein on the surface of B cells, and to CD3, a protein on T cells (the body’s own immune cells). This binding activates T cells and directs them directly to the cancer cells to destroy them. This form of therapy is particularly promising for patients in whom other treatments have been unsuccessful.

The goal of the SYRUS study (Phase 1/2 study) is to investigate the novel drug AZD0486 as a standalone therapy (monotherapy) for B-ALL. First, a well-tolerated dose will be determined (Phase 1), and then the therapy’s effectiveness will be assessed (Phase 2). The drug is administered as an intravenous infusion and has not yet been approved for the treatment of ALL. The study is divided into three parts. In Part A, the drug dose is gradually increased to determine a safe dose range based on potential side effects. To determine the optimal dose, patients in Part B of the study will be randomly assigned to two groups and treated with different doses of AZD0486. In Part C, this established dose will be tested in a larger group of patients. The study is open-label, meaning that both the medical staff and the patient know which drug is being administered. Treatments and follow-up examinations as part of the study will take place over a period of up to 3 years, during which the efficacy of the therapy and the occurrence of side effects from the various medications will be evaluated. A key factor is whether or when the disease progresses again during therapy.

Patients with CD19-positive B-ALL aged 12 to 80 years are eligible to participate in this study (Part A: ages 16 and older; Parts B and C: ages 12 and older). The disease must have been previously treated and must be either recurrent or refractory. The central nervous system (CNS) must not be affected.