OT2-05-05: Phase I/II Study of Adoptive T Cell Therapy Following In Vivo Priming with a HER2 Peptide-Based Vaccine in Patients with Stage IV Breast Cancer.
Authors: Parker SL , Higgins DM , Childs JS , Dang Y , Guthrie KA , Disis ML , Salazar LG , Coveler A 
Published: June 2012

Abstract
Background
Adoptive T cell therapy has evolved from preclinical setting to a potentially feasible treatment strategy for advanced breast cancer (BC). However, the ability to expand tumor antigen specific T cells ex vivo has been one of the major hurdles that has limited clinical translation of adoptive T cell therapy. Tumor specific T cells are rare in unprimed patients and generating large bulk cultures from rare precursor frequencies is difficult. We have found immunizing HER2+ patients to increase tumor specific T cell precursor frequencies to the levels of a vaccinated foreign antigen markedly improves the ability to generate large numbers of tumor specific T cells in vitro. We hypothesize that T cell expansion strategies that are facilitated by prior immunization will be clinically useful in the treatment of advanced BC.
Design: A Phase I/II non-randomized, single arm study. Priming with a HER2 ICD vaccine will be performed at 1 week intervals for a total of 3 vaccines. Patients will undergo leukapheresis 2 weeks after the 3rd vaccine to collect PBMC for T cell expansion. Patients will be pre-treated with cyclophosphamide 24 hours prior to 1st T cell infusion and then receive up to 3 dose-escalating infusions of T cells given 7–10 days apart. Three HER2 vaccine booster immunizations will then be administered at 1, 2, and 4 months after the final T cell infusion. Follow-up for persistent and continued immunity will then ensue.
Aims: To evaluate the safety of infusing escalating doses of HER2 specific T cells into patients with advanced HER2+ BC using ex vivo expanded autologous T cells, to investigate to what extent HER2 specific T cell immunity can be boosted or generated in individuals after infusion of HER2 specific T cells, to evaluate how long T cell immune augmentation persists in vivo after adoptive transfer of HER2 specific T cells and subsequent booster immunizations.
Criteria: Patients with HER2+ Stage IV BC who: have been maximally treated and not achieved a complete remission, have stable or slowly progressive disease, HER2+, and have adequate LVEF.
Statistical Methods: Toxicity will be determined by chemical and clinical parameters evaluated at various time points. If the true probability of a DLT is 0.11, then the probability of observing 0 DLT's in 20 patients is 0.097. If the true probability of a DLT is 0.18, then the probability of observing ≤1 DLT's in 20 patients is 0.102, and if the true probability of a DLT is 0.27, then the probability of observing ≤2 DLT's in 20 patients is 0.064. Therefore, with low observed rates of DLT (≤10%), we can be reasonably confident (∼90%) with 20 patients that the true DLT rate is &lt; 0.27. Immunologic response, defined as the successful boosting of precursor frequency with infusion of HER2−specific T cells, will be evaluated by assessing the change in T cell level from baseline. To assess the durability of the T cell response, we are primarily interested in estimating the proportion of patients whose T cells persist at a level the same or greater as the level after the final T cell infusion as long as 6 months following the final booster vaccine.
Accrual: Target=20/Actual=14
Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr OT2-05-05.