glembatumumab vedotin

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Ligands
glembatumumab vedotin

GtoPdb Ligand ID: 8926

Synonyms: CDX-011 | CR011-vcMMAE

Comment: Glembatumumab vedotin is a fully human anti-gpNMB (transmembrane glycoprotein NMB; gene symbol GPNMB) monoclonal antibody-drug conjugate (ADC) carrying the antineoplastic toxin monomethyl auristatin E (MMAE; PubChem CID 11542188). Development and preclinical evaluation of this ADC is reported in [4].
Annotated peptide sequences for this antibody are available from its IMGT/mAb-DB record.

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Summary of Clinical Use
Glembatumumab vedotin is being evaluated in Phase 2 clinical trials in patients with locally advanced or metastatic breast cancer (including a trial looking specifically at gpNMB over-expressing triple negative breast cancer), unresectable stage III or stage IV melanoma (including a separate stage IV uveal melanoma study), and recurrent osteosarcoma. US FDA has granted Fast Track designation to this ADC for the treatment of advanced, refractory or resistant gpNMB-expressing breast cancer.

Summary of Clinical Use

Glembatumumab vedotin is being evaluated in Phase 2 clinical trials in patients with locally advanced or metastatic breast cancer (including a trial looking specifically at gpNMB over-expressing triple negative breast cancer), unresectable stage III or stage IV melanoma (including a separate stage IV uveal melanoma study), and recurrent osteosarcoma.
US FDA has granted Fast Track designation to this ADC for the treatment of advanced, refractory or resistant gpNMB-expressing breast cancer.

Mechanism Of Action and Pharmacodynamic Effects
gpNMB expression is abundant in triple negative breast cancers [2], where it is a prognostic marker of shorter metastasis-free survival times. In breast cancer cells gpNMB can promote cell migration, invasion, and metastasis in vitro and in vivo [2-3]. gpNMB is also expressed in aggressive melanoma [4] and glioblastoma multiforme [1] tissue samples. Once internalised by gpNMB-expressing cells, the MMAE is cleaved [4], and the active toxin induces G₂-M cell cycle arrest which is followed by apoptotic cell death.

Mechanism Of Action and Pharmacodynamic Effects

gpNMB expression is abundant in triple negative breast cancers [2], where it is a prognostic marker of shorter metastasis-free survival times. In breast cancer cells gpNMB can promote cell migration, invasion, and metastasis in vitro and in vivo [2-3]. gpNMB is also expressed in aggressive melanoma [4] and glioblastoma multiforme [1] tissue samples.
Once internalised by gpNMB-expressing cells, the MMAE is cleaved [4], and the active toxin induces G₂-M cell cycle arrest which is followed by apoptotic cell death.