A Phase II Study of Anti-CD3 x Anti-HER2/Neu Armed Activated T Cells After Second Line Chemotherapy in Women With HER2/Neu (0, 1+ or 2+) Metastatic Breast Cancers
- To determine whether treatment with anti-CD3 x anti-HER2/neu bispecific antibody-armed
activated T-cells (ATC) after second-line chemotherapy and lymphodepletion using
cyclophosphamide improves median progression-free survival (PFS) by 3 months beyond the
median PFS of 6 months reported in published trials in women with HER2/neu-negative
metastatic breast cancer.
- To confirm the toxicity profile of anti-CD3 x anti-HER2/neu bispecific antibody-armed
ATC given after second-line chemotherapy and lymphodepletion using cyclophosphamide in
- To measure functional and phenotypic changes in immune cell populations in blood and
tumor samples (if accessible) as a consequence of immunotherapy (i.e., cytokine
responses, phenotypic markers of differentiation, and antitumor cytotoxicity).
- To develop correlates between systemic or tumor site immune responses and clinical
OUTLINE: Patients receive second-line chemotherapy for 4 courses or 4 months. Beginning 4
weeks after completion of chemotherapy, patients receive 1 dose of lymphodepleting
chemotherapy comprising cyclophosphamide IV on day -7. Beginning on day 0, patients receive
an infusion of anti-CD3 x anti-HER2/neu bispecific antibody-armed activated T-cells (ATC) IV
over 30-60 minutes once a week for 3 weeks. Patients then receive a boost of anti-CD3 x
anti-HER2/neu bispecific antibody-armed ATC at 12 weeks after the 3rd ATC infusion.
Blood and tumor tissue samples may be collected periodically for biomarker and other
After completion of study therapy, patients are followed up periodically for ≥ 2 years.
Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
30 evaluable patients will be accrued in this study. There will be a two-stage phase II design, 19 patients will be accrued in the first stage. During the 1st stage, if there are 4 or fewer progression-free patients at the 1 year follow-up, then the trial will conclude early for lack of efficacy. Otherwise, 11 add'l patients will be accrued for the 2nd stage.
At one year follow up
Lawrence Lum, M.D.
Barbara Ann Karmanos Cancer Institute
United States: Food and Drug Administration
|Barbara Ann Karmanos Cancer Institute||Detroit, Michigan 48201|