A study of the drug Glofitamab as monotherapy and in combination with standard therapy in children and young adults with relapsed or refractory mature B-cell non-Hodgkin lymphoma

Mature B-cell non-Hodgkin lymphoma (NHL) is a malignant disease of the lymphatic system that affects B lymphocytes, a subtype of white blood cells that are part of the immune system. The B cells can be affected at various stages of their maturation. When they are already fully developed (mature), the condition is referred to as “mature” B-cell NHL (e.g., Burkitt lymphoma, DLBCL). The most common symptoms include swollen lymph nodes, an enlarged spleen, fatigue, exhaustion, fever, night sweats, and weight loss. The exact causes of NHL are not fully understood, but genetic mutations and environmental factors may play a role. Currently, the standard treatment for NHL consists of immunochemotherapy; a cure is often possible with this approach. However, relapses may occur after initial treatment, or the disease may become resistant to therapy (refractory).

Glofitamab is a novel, bispecific antibody that binds to specific surface proteins on cancer cells (CD20) while simultaneously binding to the body’s own immune cells (T cells, via CD3) and stimulating them to fight cancer. The drug is already approved for the treatment of relapsed and refractory NHL in adults.

The goal of the iMATRIX GLO study is to investigate the safety and efficacy of glofitamab as monotherapy and in combination with immunochemotherapy (R-ICE: rituximab + ifosfamide, carboplatin, etoposide) in children and young adults. This is a Phase 1/2 study. This means that the study will initially be conducted with a small number of participants to assess safety and determine the appropriate dosage (Phase 1). In the second phase, the drug’s efficacy will be evaluated (Phase 2). Patients will be divided into two different groups (cohorts) based on their disease stage and prior treatment. One group will receive glofitamab alone for 12 cycles of 21 days each; the other group will receive it in combination with R-ICE for 3 cycles of 21 days each. Prior to this, patients in both groups receive pretreatment with obinutuzumab, another approved anti-CD20 antibody, to reduce the risk of side effects from glofitamab. In addition, the immunotherapy drug tocilizumab may be administered as needed to further mitigate side effects. The study is open-label, meaning that medical staff and patients (or parents) know which medications are being administered. Treatment success will be evaluated after 3 cycles of 21 days each (= 2 months). Side effects will be monitored for up to 3 years after the start of the study.

Patients with relapsed or refractory, mature NHL are eligible to participate in the study: Burkitt lymphoma; Burkitt-like acute lymphoblastic leukemia (BAL, corresponding to FAB classification L3 for mature B-cell leukemia); diffuse large B-cell lymphoma (DLBCL); primary mediastinal large B-cell lymphoma (PMBCL). Patients aged 6 months to 18 years are eligible to participate in the Phase 1 study. Patients aged 6 months to 30 years may be enrolled in the Phase 2 study. Participation is not possible in cases of isolated central nervous system (CNS) involvement.