Glembatumumab vedotin

Glembatumumab vedotin (also known as CDX-011 and CR011-vcMMAE) is an antibody-drug conjugate (ADC) that targets cancer cells expressing transmembrane glycoprotein NMB (GPNMB).

In May 2010, the U.S FDA granted Fast Track 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 (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. 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 and breast cancer. Preliminary results from these trials have shown that glembatumumab vedotin has clinical activity (promotes tumor shrinkage) in both cancer types. Moreover, patients whose tumors express GPNMB respond better to glembatumumab: they have longer progression-free survival than those whose tumors do not express GPNMB.