Phase I/II Study of the Antibody-Drug Conjugate Glembatumumab Vedotin in Patients With Locally Advanced or Metastatic Breast Cancer

Purpose Glycoprotein NMB (gpNMB), a novel transmembrane protein overexpressed in 40% to 60% of breast cancers, promotes metastases in animal models and is a prognostic marker of a poor outcome in patients. The antibody-drug conjugate glembatumumab vedotin consists of a fully human anti-gpNMB monoclonal antibody, conjugated via a cleavable linker to monomethyl auristatin E. Glembatumumab vedotin is generally well tolerated, with observed objective responses in advanced melanoma. This is, to our knowledge, the first study of glembatumumab vedotin in breast cancer. Patients and Methods Eligible patients had advanced/metastatic breast cancer with at least two prior chemotherapy regimens, including taxane, anthracycline, and capecitabine. A standard 3+3 dose escalation was followed by a phase II expansion. Immunohistochemistry for gpNMB was performed retrospectively for patients with available tumor tissue. Results Forty-two patients were enrolled. Dose-limiting toxicity (DLT) consisted of worsening neuropathy...