Breast cancer is the most common malignancy in women and the significant cause of cancer-related deaths, second only to lung cancer. Amongst different subtypes of breast cancers, triple-negative breast cancer (TNBC) is especially challenging due to fewer treatment options and more aggressive clinical course. Therefore, development of molecularly targeted therapies for TNBC is crucial. Glycoprotein nonmetastatic B (GPNMB) is overexpressed in many malignancies, including TNBC, and is associated with poor prognosis. The antibody-drug conjugate (ADC) glembatumumab vedotin (CDX-011) selectively targets GPNMB and was investigated for its efficacy in metastatic breast cancer. Despite promising initial results, development of CDX-011 was discontinued in 2018 after it failed to show benefit over capecitabine in a Phase II clinical trial. This chapter reviews the mechanisms of action, preclinical and Phase I/II results of glembatumumab vedotin, lessons learned, and insights gained in the development of ADCs for the treatment of breast cancer.