Flotetuzumab, also known as MGD006, is a clinical-stage molecule currently being investigated as a treatment in a wide range of hematological malignancies, or blood cancers, such as acute myeloid leukemia (AML) and myelodysplastic syndromes (MDS).

Being developed by MacroGenics, flotetuzumab has been shown to have acceptable tolerability in patients diagnosed with AML or MDS.

How flotetuzumab works

Flotetuzumab is a humanized dual-affinity re-targeting (DART) protein. DARTs are antibody-based molecules that can bind to two distinct cell-surface molecules at the same time.

Flotetuzumab recognizes both CD3 and CD123. CD3 is a molecule produced by immune cells called T-cells, and  CD123 is a protein that is overproduced by certain types of cancer cells, including those of AML and MDS. In this way, flotetuzmab redirects T-cells to recognize and kill CD123-producing cancer cells.

Flotetuzumab in pre-clinical and clinical trials

The activity and safety of flotetuzumab were investigated in animals models of disease. The results published in the journal Science Translational Medicine revealed that flotetuzumab was effective in eliminating human AML cells implanted in mouse models in the presence of human T-cells.

Flotetuzumab was also investigated as a potential therapy for AML in cynomolgus monkeys. Results published in the scientific journal Blood showed that, when administered to these monkeys, flotetuzumab demonstrated a potent activity and was effective in eliminating circulating CD123-positive cells at doses that were considered safe and well-tolerated.

Flotetuzumab is currently being investigated in a Phase 1 dose-escalation study (NCT02152956) in patients with AML and MDS whose disease is not expected to benefit from chemotherapy.

This study’s main objective is to determine the maximum tolerated dose of flotetuzumab. It will then evaluate the pharmacokinetics (movement in the body) and pharmacodynamics (effect on the body), as well as the potential anti-tumor activity of flotetuzumab.

Results so far, presented at the European Society of Medical Oncology (ESMO) 2017 Congress, showed that flotetuzumab was well-tolerated in the dose escalation portion of the study. Flotetuzumab also showed encouraging anti-cancer activity at the “threshold dose” of 500ng/kg/day or greater in a majority of patients.

The study is ongoing and still recruiting patients in the U.S. and Europe; more information is available by clicking on its trial identification number.

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