The study seeks to establish the safety of neoadjuvant aromatase inhibitor with: DPX-Survivac, DPX-Survivac plus radiation, or DPX-Survivac with cyclophosphamide in stage I to III HR+HER2- breast cancer. There will be sequential enrollment into 3 arms with an anticipated N=6 participants per arm for N=18 participants in total. All participants will receive letrozole 2.5 mg daily during the 6 weeks of neoadjuvant therapy. Neoadjuvant therapy occurs weeks 1-6, with standard of care surgery taking place week 7 to 9.
Women with hormone receptor positive, HER2-negative (HR+/HER2-) breast cancer with large tumors or positive lymph nodes have low response rates with neoadjuvant chemotherapy. Survivin is overexpressed in HR+HER2- breast cancer. Increasing tumor-specific Th1 immunity by administration of DPX-Survivac may alter the immune environment of these tumors. Radiation is a standard component of breast cancer therapy causing a reduction in local recurrences and improved breast cancer specific survival. Low dose cyclophosphamide can deplete regulatory T-cells without altering levels of effector T-cells. The investigators predict that combining a vaccine targeting Survivin, overexpressed in HR+HER2- tumors, with other immune modulating therapies such as radiation or low dose cyclophosphamide can enhance the efficacy of DPX-Survivac. Primary Objective 1\) Safety of neoadjuvant aromatase inhibitor with: DPX-Survivac, DPX-Survivac plus radiation, or DPX-Survivac with cyclophosphamide in stage I to III HR+HER2- breast cancer Secondary Objectives 1. Immunogenicity of each arm, assessed by IFN-γ ELISPOT in PBMC. 2. Immunogenicity of each arm, assessed by GEO-Mx digital spatial profiler evaluation of FFPE tissue and TCRβ evaluation for surviving-specific T cells in the tumor. Exploratory Objectives 1. Evaluation of the % TIL in the biopsy specimen and at the time of surgery within/between arms 2. Evaluation of the Ki67 changes between the biopsy and at time of surgery within/between arms 3. Comparison of immunogenicity, TIL change, and Ki67 change across arms 4. Epitope spreading within/between arms 5. Evaluation of Triseq (germline, whole exome sequencing, and RNAseq) of the tumor immune environment within/between arms 6. Evaluation of immune environment using multi-parameter immunohistochemistry within/between arms 7. Evaluation by experimental MRI in arm that adds radiation 8. Evaluation of survivin-specific MHC-tetramer staining in PBMC
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
DPX is a novel formulation that when combined with target antigens acts to activate T cells. It is a lipid-based formulation that creates a long lasting depot at the site of injection, forcing an "active uptake" by antigen presenting cells (APCs). APCs traffic to regional lymph nodes where naïve T cells are activated, inducing strong and sustained immune responses. All arms will receive DPX-Survivac on weeks 2 and 5.
Aromatase inhibitor all arms will receive
oral chemotherapy used in the neoadjuvant setting for Arm C only
Providence Portland Medical Center
Portland, Oregon, United States
Number of participants without the following safety events: TASAEs, persistent grade III/IV TAAEs, or toxicity-related delays in curative-intent surgery. Toxicity graded by CTCAE v5.0 and monitoring of AEs performed per FDA and NCI guidelines.
yes/no outcome variable, ascertained for each individual subject, and reported as a binomial proportion for each arm. Safety will be reported for all subjects who receive at least one dose of drug/radiation/study therapy
Time frame: The safety assessment period begins with day 1 and ends within 30 days of surgical excision.
Immunogenicity of each therapeutic arm IFN-γ ELISPOT
assessed by IFN-γ ELISPOT in PBMC
Time frame: throughout the study day 1, Day 8, Day 15, Day 29, Day 36, Week 7-9, Week 11, and 6 months post-surgery
Immunogenicity of each therapeutic arm GEO-Mx digital spatial profiler
assessed by GEO-Mx digital spatial profiler evaluation of Formalin-Fixed, parafin-embedded (FFPE) tumor and TCRβ evaluation for surviving-specific T cells in the tumor
Time frame: throughout the study day 1, Day 8, Day 15, Day 29, Day 36, Week 7-9, Week 11, and 6 months post-surgery
This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.
Purpose
TREATMENT
Masking
NONE
Enrollment
6
Directed radiation at week 4 for Arm B only