Glembatumumab vedotin is an antibody-drug conjugate

Antibody-drug conjugate

Antibody-drug conjugates are a new type of targeted therapy, used for example for cancer. They consist of an antibody linked to a payload drug . Hence, they are a type of immunoconjugate and often an immunotoxin.The antibody causes the ADC to bind to the target cancer cells...

 (ADC) that targets cancer cells expressing transmembrane glycoprotein NMB (GPNMB).

In May 2010, the U.S FDA

Food and Drug Administration

The Food and Drug Administration is an agency of the United States Department of Health and Human Services, one of the United States federal executive departments...

 granted Fast Track

Fast Track

Fast Track is an informal English phrase meaning "the quickest and most direct route to achievement of a goal, as in competing for professional advancement".Fast Track may also refer to:* Fast Track, a FoxBusiness.com show hosted by Anna Gilligan...

 designation to CDX-011 for the treatment of advanced, refractory or resistant GPNMB-expressing breast cancer.

Structure and mechanism

The fully human monoclonal antibody glembatumumab (CR011) is linked to monomethyl auristatin E

Monomethyl auristatin E

Monomethyl auristatin E is a synthetic antineoplastic agent. Because of its toxicity, it cannot be used as a drug itself; instead, it is linked to a monoclonal antibody which directs it to the cancer cells...

 (MMAE).

The linkage is stable in the bloodstream. The antibody binds to GPNMB on the cancer cells, the ADC is internalised, the linkage is broken and MMAE is released to kill the cell.

In preclinical studies glembatumumab vedotin was capable of killing GPNMB expressing melanoma and breast cancer cells in vitro and inducing partial or complete regression of GPNMB-expressing tumors in mouse models.

Clinical trials

In September 2010 a Phase 2b clinical study started of glembatumumab vedotin in 120 patients with GPNMB-expressing breast cancer including those with triple negative breast cancer

Triple Negative Breast Cancer

Triple-negative breast cancer refers to any breast cancer that does not express the genes for estrogen receptor , progesterone receptor or Her2/neu. Triple negative is sometimes used as a surrogate term for basal-like, however more detailed classification is possible providing better guidance for...

. Preliminary results are expected in the last quarter of 2011.

, glembatumumab vedotin is being investigated in Phase I/II clinical trials for the treatment of advanced melanoma

Melanoma

Melanoma is a malignant tumor of melanocytes. Melanocytes are cells that produce the dark pigment, melanin, which is responsible for the color of skin. They predominantly occur in skin, but are also found in other parts of the body, including the bowel and the eye...

 and breast cancer

Breast cancer

Breast cancer is cancer originating from breast tissue, most commonly from the inner lining of milk ducts or the lobules that supply the ducts with milk. Cancers originating from ducts are known as ductal carcinomas; those originating from lobules are known as lobular carcinomas...

. Preliminary results from these trials have shown that glembatumumab vedotin has clinical activity (promotes tumor shrinkage) in both cancer types. Patients whose tumors express GPNMB respond better to glembatumumab and have longer progression-free survival than those whose tumors do not express GPNMB.