A phase Ib study of pre-operative, locoregional IRX-2 cytokine immunotherapy to prime immune responses in patients with early stage breast cancer.

Purpose: To evaluate the safety and feasibility of pre-operative locoregional cytokine therapy (IRX-2 regimen) in early stage breast cancer, and to evaluate for intratumoral and peripheral immunomodulatory activity. Experimental Design: Sixteen patients with stage I-III early stage breast cancer (any histology type) indicated for surgical lumpectomy or mastectomy were enrolled to receive pre-operative locoregional immunotherapy with the IRX-2 cytokine biologic (2mL subcutaneous x 10 days to peri-areolar skin). The regimen also included single-dose cyclophosphamide (300mg/m2) on day 1 to deplete T-regulatory cells, and oral indomethacin to modulate suppressive myeloid subpopulations. The primary objective was to evaluate feasibility (i.e. receipt of therapy without surgical delays or grade III/IV treatment-related adverse events). The secondary objective was to evaluate changes in stromal tumor infiltrating lymphocyte score. The exploratory objective was to identify candidate pharmacodynamic changes for future study using a variety of assays including flow cytometry, RNA and T-cell receptor DNA sequencing, and multispectral immunofluroescence. Results: Pre-operative locoregional cytokine administration was feasible in 100% (n=16/16) of subjects and associated with increases in stromal tumor-infiltrating lymphocytes (p