Abstract 2806: A phase Ia/Ib trial of chemotherapy followed by infusions of activated T cells armed with OKT3 x trastuzumab bispecific antibody, IL-2 and GM-CSF for stage II/ III, Her2+ or Her2- high risk breast cancer (more than 10+ nodes)

Abstract

Abstract Background: Anti-CD3 x anti-HER2Bi bispecific antibody (HER2Bi) targeted monoclonal antibody (mAb) activated T cells (ATC) exhibit anti-HER2 cytotoxicity, proliferate, and secrete immunokines upon tumor engagement. This study reports a phase I immunotherapy trial in 9 women with locally advanced breast cancer consisting of infusions of HER2Bi armed ATC (aATC) in combination with interleukin 2 (IL-2) and granulocyte-macrophage-colony stimulating factor (GM-CSF) to evaluate safety, feasibility, time to progression (TTP), overall survival (OS), T cell trafficking, and immune responses. Methods: ATC were produced by stimulating peripheral blood mononuclear cells (PBMC) obtained by leukapheresis with anti-CD3 monoclonal antibody and expanding the ATC in IL-2. ATC were harvested, armed with HER2Bi and cryopreserved in aliqouts. Groups of 3 patients received 20, 40, 80 or 160 x 109 aATC per infusion twice a week for four weeks(Table 1). Results: Eight of 9 patients were ER positive, 2 of 9 were Her 2 overexpressing tumors. The median OS for all patients was 103.5 months (14.3 to 134.7months). Six of 9 patients are alive. Four out of the six patients have no evidence of disease and 2 patients relapsed (one at 77.27 months and the other at 104.67months). It was feasible to grow up to 160 x 109 ATC and both patients assigned to this dose level were able to reach it. There were no cell-based dose limiting toxicities. aATC persisted in the blood for at least a week. aATC infusions induce cellular anti-tumor responses and cytokine responses. Interpretation: Targeting Her2 positive and negative tumors induced cytotoxic anti-tumor responses, increases in Th1 cytokines and IL-12 serum levels, clinical responses that suggest aATC infusions provided a survival benefit. These results are being confirmed in a phase II trial for metastatic breast cancer. Table 1Planned doseActual Dose20Bill21.640Bill42.7540Bill37.640Bill42.480 Bill80.080Bill70.3580Bill96.0160Bill176.75160Bill160.0 Citation Format: Deepa B. Jagtap, Ritesh Rathore, Archana Thakur, Gerald Colvin, Nicola Kouttab, Abby Maizel, Abhinav Deol, Lawrence G. Lum. A phase Ia/Ib trial of chemotherapy followed by infusions of activated T cells armed with OKT3 x trastuzumab bispecific antibody, IL-2 and GM-CSF for stage II/ III, Her2+ or Her2- high risk breast cancer (more than 10+ nodes). [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 2806. doi:10.1158/1538-7445.AM2014-2806