Correlation of GPNMB expression with outcome in breast cancer (BC) patients treated with the antibody–drug conjugate (ADC), CDX-011 (CR011-vcMMAE).

Document Type

Article

Department

Haematology and Oncology, East Africa

Abstract

Background: GPNMB (osteoactivin), a novel glycoprotein expressed in 25-40% of breast cancers as well as various tumor types, promotes BC metastases in vivo and is a prognostic marker of poor outcome in BC patients (pts). CDX-011, an ADC consisting of a fully-human monoclonal antibody to GPNMB (CR011) conjugated via enzyme-sensitive linker to the potent cellular toxin MMAE, has been studied in two phase I/II studies in metastatic melanoma and BC. As previously reported, CDX-011 was safe and active, with objective responses observed and the primary efficacy endpoints met for both studies. We have analyzed tumor samples from the BC study to examine the correlation of GPNMB expression with clinical outcome.

Methods: Standard 3+3 dose-escalation followed by an expanded phase II assessing 12- week progression-free survival (PFS) (P0=≤10%; P1=≥30%; α=β=0.10). Immunohistochemistry for GPNMB was performed on biopsy samples for a subset of pts using a polyclonal goat anti-GPNMB antibody and a biotin-conjugated donkey anti-goat secondary antibody. Sections were developed with DAB and counterstained with hematoxylin. Samples with ≥5% expression of GPNMB were considered positive.

Results: 42 pts were enrolled. 10/14 (71%) tumor specimens available/analyzed to date were positive for GPNMB. These included both tumor stroma and/or epithelial expression of GPNMB. Activity data are shown in the Table. Two pts had confirmed PR (durations of 27 and 30+ weeks); both were GPNMB positive.

Conclusions: CDX-011 is active in heavily pretreated, advanced BC pts. In a subset of pts analyzed, GPNMB was frequently expressed and expression of GPNMB was associated with improved outcomes following treatment with CDX-011. A clinical study focused on BC pts with tumors expressing GPNMB is planned.

Comments

This work was published before the author joined Aga Khan University.

Publication (Name of Journal)

Journal of Clinical Oncology

DOI

https://doi.org/10.1200/jco.2010.28.15_suppl.1095

Creative Commons License

Creative Commons Attribution 4.0 International License
This work is licensed under a Creative Commons Attribution 4.0 International License.

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