Two new CAR-T cell therapies for the treatment of previously treated B-cell lymphomas

B-cell lymphomas are a type of non-Hodgkin lymphoma and affect B lymphocytes, a subtype of white blood cells that are part of the immune system. B-cell lymphoma is an umbrella term for various malignant diseases of the lymphatic system, and symptoms include swollen lymph nodes, an enlarged spleen, fever, night sweats, and weight loss. The exact causes of these diseases are not yet fully understood, but genetic mutations and infections may play a role. Patients with newly diagnosed B-cell lymphoma are typically treated with immunochemotherapy; radiation therapy is also used in certain situations. If the disease cannot be controlled with the current therapy (refractory) or if a relapse occurs, the treatment is changed. CAR-T cell therapy represents a novel treatment option in this context. As part of this therapy, the patient’s own immune cells (T cells) are harvested and genetically modified so that they help the immune system recognize and destroy cancer cells once they are reinfused into the patient via a vein. Various studies on CAR-T cells have already been conducted in recent years, and the basic principle has essentially always been as described above.

The goal of this Phase 1 study is to investigate the efficacy, safety, and optimal dose of the drugs KITE-363 and KITE-753. These are two different CAR-T cell drugs that function in nearly identical ways. Neither drug has been approved yet. In Phase 1a of the study, patients first receive chemotherapy with cyclophosphamide and fludarabine. Subsequently, patients will receive either KITE-363 or KITE-753, each as a single dose at a predefined dose (dose escalation). Depending on tolerability, the dose will be increased for subsequent patients. The optimal dose of the active ingredients determined in this phase will be tested in a larger group during Phase 1b (dose expansion). The study is open-label, meaning that both the medical staff and the patient know which drug is being administered. The CAR-T cells are administered as a single dose. Follow-up visits as part of the study will take place for up to 15 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. The primary endpoint in Phase 1a of the study is the occurrence of dose-limiting side effects up to 28 days after treatment. The primary endpoint in Phase 1b is the response rate to therapy.

Women and men aged 18 and older with B-cell lymphoma are eligible to participate in this study. The specific subtype of B-cell lymphoma is not specified. The disease must have been previously treated and must be refractory or show signs of recurrence. There must be no involvement of the central nervous system, and patients must not have previously undergone stem cell transplantation.