Study on the Safety and Efficacy of the Drug AZD0486 (bispecific antibody) in Previously Treated Patients with Certain B-Cell Cancers (CLL/SLL, MCL, LBCL)

Chronic lymphocytic leukemia (CLL), including the subtype small lymphocytic lymphoma (SLL), mantle cell lymphoma (MCL), or large B-cell lymphoma (LBCL) are among the so-called mature B-cell malignancies. These are cancers of the blood or lymphatic system in which certain white blood cells (B lymphocytes) multiply uncontrollably. The exact causes are not yet fully understood, but genetic changes and environmental factors often play a role. Typical symptoms include fatigue, anemia, weight loss, and swollen lymph nodes. Current treatment often consists of a combination of targeted drugs, such as Bruton’s tyrosine kinase inhibitors (BTK inhibitors), immunotherapies like rituximab, or traditional chemotherapies, such as the classic R-CHOP regimen (rituximab + cyclophosphamide, doxorubicin (hydroxydaunorubicin), vincristine (Oncovin®), and prednisone). Many patients initially respond well to these therapies; however, some experience relapses or develop resistance to these treatments (refractory).

The investigational drug AZD0486 is a so-called bispecific T-cell engager. It was developed to specifically activate the body’s own immune system against cancer cells. It does this by simultaneously binding to the surface marker CD19 on B cells and to CD3 on T cells, thereby bringing the immune cells into direct contact with the cancer cells and stimulating them to destroy the cancer cells in a targeted manner.

The goal of the Soundtrack E study is to investigate AZD0486 either alone or in combination with other active substances. The study is divided into three sub-studies, each targeting different groups of patients. Substudy 1 will enroll patients with chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL). There are two cohorts here: In Cohort 1A, patients receive AZD0486 as a single treatment (monotherapy), while in Cohort 1B, AZD0486 is administered in combination with the BTK inhibitor acalabrutinib. Substudy 2 is designed for patients with mantle cell lymphoma (MCL). Here, too, there are two cohorts: one for monotherapy with AZD0486 (Cohort 2A) and one for the combination with acalabrutinib (Cohort 2B). Substudy 3 treats patients with diffuse large B-cell lymphoma (DLBCL). These patients receive AZD0486 in combination with the standard R-CHOP chemotherapy regimen. Treatment consists of multiple cycles, the exact duration of which depends on the individual’s response to therapy. Patients will be followed for up to 6.5 years to collect both short-term and long-term data on the safety and efficacy of the treatment. The goal is to determine the best-tolerated dose of AZD0486 and to evaluate its efficacy as a monotherapy or in combination with other medications. The study is open-label, meaning that medical staff and patients know which medications they are receiving, and it is divided into a screening phase (28 days), a treatment phase, and a follow-up phase.

Patients aged 18 and older are eligible to participate. Eligibility criteria include, among other things, good general health (ECOG 0–2), a confirmed diagnosis of one of the listed diseases, and certain prior treatments. Depending on the sub-study, specific requirements regarding previous therapy apply. Patients are excluded if they have, among other things, central nervous system involvement (e.g., brain lymphomas), certain heart conditions, recent radiation therapy, prior CAR-T cell therapy, or severe side effects from previous immunotherapies. Certain comorbidities or medications may also preclude participation.

Facts

1. Which disease: Chronic lymphocytic leukemia (CLL), small lymphocytic lymphoma (SLL), mantle cell lymphoma, large B-cell lymphoma.
2. Cancer characteristics: Recurrent or treatment-resistant disease following prior treatment.
3. What the study investigates: The efficacy and safety of AZD0486 alone or in combination with a BTK inhibitor or R-CHOP.
4. Study objective: To evaluate the side effects, tolerability, and efficacy of the drug.
5. Study duration: Up to 6 years; the first treatment phase lasts approximately 2 months.
6. Study characteristics: Three sub-studies, different treatment arms, no blinding.