Pilot Study of Glembatumumab Vedotin Following Doxorubicin and Cytoxan as Neo-adjuvant Therapy in Gp-NMB-expressing High Risk Triple Negative Breast Cancer

1. Willingness and ability to provide written informed consent and to comply with the study protocol as judged by the investigator.

2. Patients diagnosed with triple negative breast cancer, (stages II-III, or high risk T1c disease) found to have gpNMB expression at or above 25%), and who are appropriate candidates for neo-adjuvant therapy. Patients must be willing to undergo lumpectomy (with radiation therapy) or mastectomy following neo-adjuvant therapy.

3. Subjects may be female or male.

4. ECOG Performance Status of 0-2.

5. Age ≥ 18 years.

6. Subject must have a life expectancy ≥ 6 months.

7. Absolute neutrophil count ≥ 1,500 cells/mm3

8. Platelets ≥ 100,000 cells/mm3

9. Hemoglobin ≥ 9g/dl (Note: The use of transfusion to achieve Hemoglobin ≥ 9 g/dl is acceptable)

10. Serum creatinine OR GFR ≤ 1.5 x institutional upper limit normal (IULN)

11. Bilirubin ≤ 1.5 x IULN OR Direct Bilirubin ≤ULN for patients with total bilirubin levels \>1.5×ULN

12. ALT and AST ≤ 2.5 IULN

13. Alkaline phosphatase ≤ 2.5 IULN

14. Women of childbearing potential (WOCBP) and men must agree to use adequate contraception prior to study entry and for at least 1 year following last dose of study drug.

a. WOCBP includes any female who has experienced menarche and who has not undergone successful surgical sterilization (hysterectomy, bilateral tubal ligation or bilateral oophorectomy) or is not postmenopausal \[defined as amenorrhea ≥ 12 consecutive months; or women on hormone replacement therapy with documented serum follicle stimulating hormone (FSH) level \> 35 mIU/mL\]

i. Prior to study enrollment, WOCBP must be advised of the importance of avoiding pregnancy during trial participation and for at least 1 year following participation and the potential risk factors for an unintentional pregnancy

ii. The following birth control methods are allowed during the study: Barrier methods (Intra-uterine device (IUD), Diaphragm with spermicide, Cervical cap with spermicide, Condom with spermicide) or Abstinence (no heterosexual activity)

b. Non-vasectomized males must agree to use adequate contraception for at least 120 days after the last dose of study drug

i.The following birth control methods are allowed during the study: Partner is not WOCBP or is taking hormonal contraceptives, Barrier methods (Intra-uterine device (IUD), Diaphragm with spermicide, Cervical cap with spermicide, Condom with spermicide) or Abstinence (no heterosexual activity)

ii. Males must also abstain from sperm donations for at least 120 days after the last dose of study drug

What this study is about