Novel Targeted Therapy for Refractory Breast Cancer

A recent study of a novel antibody-drug conjugate (ADC) in patients with refractory breast cancer may be the next generation of targeted therapy. Glembatumumab vedotin (CDX-011) is an ADC that targets and binds to glycoprotein NMB (gpNMB), a protein expressed by multiple tumor types. Overexpression of gpNMB has been shown to promote the growth and metastasis of breast cancer subtypes that are associated with poor clinical outcomes. This new therapeutic approach delivers cytotoxic agents directly to the tumor.

EMERGE is a randomized phase II study of glembatumumab vedotin in patients with advanced glycoprotein NMB–expressing breast cancer. The results were published in the April 6, 2015 issue of the Journal of Clinical Oncology (JCO). Patients with gpNMB- expressing breast cancer were studied to evaluate whether the activity of glembatumumab vedotin was dependent on gpNMB expression.

"These data supported the initiation of the METRIC study in patients with triple-negative breast cancer-where gpNMB overexpression is seen in approximately 40% of patients. We believe gpNMB could be an important marker in breast cancer and that glembatumumab vedotin holds significant potential as a possible targeted therapy for women facing this disease," said Thomas Davis, MD, Executive Vice President and Chief Medical Officer of Celldex Therapeutics, in a press release.

Additional analyses performed to evaluate activity by gpNMB expression pattern were revealing in some groups of patients, specifically those with TNBC and/or higher levels of tumor NMB expression. One subset of patients was included to determine whether epithelial expression of gpNMB, a negative prognostic indicator for breast cancer recurrence, has an impact on the outcome with glembatumumab vedotin.

Denise A. Yardley, MD, first author on the JCO article and Robert Weaver, MD, and colleagues concluded that glembatumumab vedotin is well tolerated in heavily pretreated patients with breast cancer. The primary end point in advanced gpNMB-expressing breast cancer was not met for all enrolled patients (median tumor gpNMB expression, 5%); activity may be improved in patients with gpNMB-overexpressing tumors and/or TNBC.

The phase II METRIC (Metastatic Triple-Negative Breast Cancer) trial for patients with refractory breast cancer is currently underway.

References:

• Yardley DA, Weaver R, Melisko ME, et al. (2015). EMERGE: A Randomized Phase II Study of the Antibody-Drug Conjugate Glembatumumab Vedotin in Advanced Glycoprotein NMB–Expressing Breast Cancer. Journal of Clinical Oncology.
• Celldex Therapeutics. (2015). Celldex Therapeutics' Phase 2 EMERGE Study of Glembatumumab Vedotin in Metastatic Breast Cancer Published in Journal of Clinical Oncology.