Abstract OT1-01-01: A phase I trial of the safety and immunogenicity of a multiple antigen vaccine (STEMVAC) in HER2 negative advanced stage breast cancer patients
Authors: Higgins DM , Childs JS , Salazar LG , Disis ML 
Published: May 2016

Abstract
Background: Biologically relevant epithelial to mesenchymal transformation (EMT) associated proteins, a subpopulation of tumor cells with stem like properties, have been identified and are responsible for tumor initiation, metastasis formation and resistance to cancer therapies involved in breast cancer (BC) initiation. It is hypothesized that the acquisition of stem cell properties is driven by EMT induction and that BC stem cells express EMT-associated proteins. A vaccine which would educate the immune system to recognize and eliminate cells that have up-regulated proteins associated with BC stem cells/EMT could eradicate BC at the time of initiation or relapse. We have identified 5 stem cell/EMT proteins that are immunogenic in BC patients and created a vaccine, STEMVAC, composed of extended Th1 epitopes derived from these proteins. STEMVAC is safe and inhibits tumor growth in preclinical murine studies.
Trial design: Phase I dose escalation study evaluating 3 doses of STEMVAC admixed with 100 mcg of GMCSF. Patients enrolled sequentially into 1 of 3 dose arms (10 patients/arm): Arm 1=150 mcg, Arm 2=300 mcg, and Arm 3=600 mcg. 3 patients must complete 3 monthly vaccines and month 4 evaluation with no dose limiting toxicity before further accrual to that arm. Patients may receive 2 boosters, 3 and 9 months after their 3rd vaccine. Toxicity is assessed at baseline through end of study. Serial blood draws for immunologic monitoring is done.
Eligibility criteria: Stage III-IV HER2 negative BC patients treated with standard therapy who: (1) are without evidence of disease or have stable bone-only disease, (2) are 28 days from last chemotherapy, radiotherapy, systemic steroids, (3) have adequate blood counts, (4) have no active autoimmune disease. Endocrine therapy and bisphosphonates are allowed.
Specific aims: (1) Determine the safety of 3 escalating doses of STEMVAC, (2) Determine the most immunogenic dose, (3) Determine whether a STEMVAC Th1 polyepitope plasmid based vaccine elicits persistent T cell memory, and (4) Evaluate if STEMVAC modulates T regulatory and myeloid derived suppressor cells.
Statistical methods: Safety will be determined by laboratory and clinical parameters. Descriptive statistics will be used to summarize changes from baseline. Safety benchmarks to move to the next arm will be grade 3 toxicity rate of ≤ 15% and grade 4 toxicity rate of ≤ 5% in the first 3 vaccinations. Immunogenicity evaluated by generation of antigen specific Th1 immunity via ELISPOT. Immunologic efficacy is defined as achievement of significant increase in Th1 immunity for ≥50% of the immunizing antigens compared to baseline; and a greater proportion of patients developing T-cell immunity to a greater number of the antigens included in the vaccine. Exploratory analysis will be used to assess memory Th1 dominant immune response to all 5 antigens. Treg and MDSC will be defined as present or absent, and the probability of each will be estimated as a simple proportion.
Target accrual: 30 patients-no patients accrued to date.
Citation Format: Higgins DM, Childs JS, Salazar LG, Disis ML. A phase I trial of the safety and immunogenicity of a multiple antigen vaccine (STEMVAC) in HER2 negative advanced stage breast cancer patients. [abstract]. In: Proceedings of the Thirty-Eighth Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2015 Dec 8-12; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(4 Suppl):Abstract nr OT1-01-01.