It is a humanized dual-affinity re-targeting (DART) protein. DART proteins are antibody-based molecules that can simultaneously bind to two distinct molecules on the surface of cells.
How MGD009 works
Unlike traditional monoclonal antibodies that target and bind to a single antigen (a foreign substance that triggers an immune response), DART proteins are bispecific antibody-based molecules that can target and bind to two antigens at the same time.
MGD009 is designed to target and bind to the B7-H3 antigen found on tumor cells, and to the CD3 antigen present on T-cells. It also contains a mutated Fc domain – a structure responsible for antibodies’ natural immune functions – to allow a higher stability and longer half-life in the circulation.
By binding to B7-H3 on tumor cells and CD3 on T-cells, MGD009 cross-links the T-cells with B7-H3-producing tumor cells, thereby activating and redirecting the immune system to eliminate and block the growth of B7-H3-producing tumor cells.
MGD009 in clinical trials
MGD009 was first evaluated in preclinical studies conducted in human cell lines, and mouse and monkey models. Results from these studies showed that MGD009 enables the death of B7-H3-producing human cancer cell lines by T-cells. They also showed that it leads to the prevention of tumor growth and the regression of B7-H3-producing tumors in mice. MGD009 also demonstrated a prolonged half-life (five to six days) when injected into monkeys.
The safety, tolerability, pharmacokinetics (movement in the body), pharmacodynamics (effect on the body), and efficacy of MGD009 are currently being evaluated in a dose escalation, first-in-human Phase 1 clinical trial (NCT02628535). The trial is recruiting an estimated 118 patients with several types of B7-H3-producing tumors in eight locations in the U.S. It will be conducted in two parts: a dose escalation part and a cohort expansion part.
In the dose escalation part, patients will be treated every two weeks with escalating doses of MGD009 injected into a vein starting at a dose of 0.3 micrograms per kg body weight. In the cohort expansion part, patients will be treated with the maximum tolerated dose determined in the dose escalation part.
The study also includes a survival follow-up phase consisting of a two-year period after the final dose of the study drug is administered. The trial is expected to be completed by December 2020.
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