Amgen Corporation announced updated results from its Phase 2 study with blinatumomab. Blinatumomab is a specially produced antibody that targets a protein called “CD19.” This antibody is made by an engineered cell line that produces one and only one kind of antibody. Such an antibody is called a “monoclonal antibody.” Monoclonal antibodies are made by antibody-making cells (B-lymphocytes) that are fused to tumor cells. The tumor cell immortalizes the B lymphocyte and this immortal cell now makes one type of antibody for its entire existence. Such a cell line that results from the fusion of a tumor cell with a B lymphocyte is called a “hybridoma” cell line.
CD19 is a cell surface protein that is made on the surfaces of B lymphocytes. Because B lymphocytes can over-grow and form blood-based tumors, an antibody that binds tightly to CD19 can specifically target B lymphocyte-based tumors. The binding of such antibodies also alerts other immune cells (T cells) to home to those cells and destroy them.
Blinatumomab, however, is an even more special molecule, because it binds CD19 at one end of the protein and a T cell-specific protein called CD3. Blinatumomab, therefore, acts as a bridge between tumor cells and T cells. It helps the T cells recognize the tumors as foreign. It is therefore an unusual type of chemotherapeutic agent called a bi-specific T-cell engager or BiTE. Another BiTE is MT110:, which is used to treat gastrointestinal and lung cancers, and is directed against the EpCAM antigen and the T cell surface protein B3.
Treatment with blinatumomab helped achieve a high-rate of complete response (CR) in 72% of all adult patients who were diagnosed with relapsed or refractory B-precursor acute lymphoblastic leukemia (ALL), and were treated in the study.
Full results of the study will be presented at the 48th Annual Meeting of the American Society of Clinical Oncology (ASCO) on June 4, 2012.
For more information on this Phase 2 single-arm dose-ranging clinical trial, 26 of the 36 patients treated with blinatumomab (across all of tested doses and schedules) achieved a complete response with partial recovery of their blood cell counts. All but two patients achieved a “molecular response..” Molecular response means that the presence of leukemic cells were not detectable with polymerase chain reaction (PCR) assays. There were also not treatment-related deaths or serious adverse events reported in this study.
Median survival was 9.0 (8.2, 15.8) months with a median follow-up period of 10.7 months at the time of the analysis. In the group of patients who received the selected dose of blinatumomab, the median survival time was 8.5 months, and the median duration of response in the 26 patients who responded to treatment was 8.9 months.
Max Topp, department of internal medicine II, University of Wuerzburg and chair of the study, said: “For these patients with limited treatment options, the remission rate observed in the trial is a vast improvement over the current standard of care. These results also represent significant progress in our research of immunotherapies; a new approach to fighting cancer that we believe could make a real difference for patients.”
Patients who received the selected dose and schedule, the most common adverse events were mild and included fever, (70%), headache (39%), shaking (30%) and fatigue (30%). Reversible central nervous system events led to treatment interruptions in six patients with two patients permanently discontinuing treatment.