NCT04895761

Neoadjuvant DPX-Survivac Aromatase Inhibition, Radiotherapy or Cyclophosphamide in HR+HER2- Breast Cancer

Phase Ib Study of Neoadjuvant DPX-Survivac, Aromatase Inhibition, and With/Without Radiotherapy or Cyclophosphamide in HR+HER2- Breast Cancer

• Status: Active Not Recruiting
• Phase: Phase 1
• Study type: Interventional
• Enrollment: 6 (actual)
• Sponsor: Providence Health & Services · Academic / Other
• Sex: Female
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

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.

Detailed description

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

Conditions

• Breast Cancer

Interventions

Type	Name	Description
BIOLOGICAL	DPX-Survivac	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.
DRUG	Letrozole 2.5mg	Aromatase inhibitor all arms will receive
DRUG	Cyclophosphamide 50mg	oral chemotherapy used in the neoadjuvant setting for Arm C only
RADIATION	XRT 10Gy x2	Directed radiation at week 4 for Arm B only

Timeline

• Start date: 2021-09-10
• Primary completion: 2023-06-16
• Completion: 2026-09-01
• First posted: 2021-05-20
• Last updated: 2026-04-13

Locations

1 site across 1 country: United States

Regulatory

• FDA-regulated drug study