Safety and immunogenicity of a tri-antigen vaccine targeting IGFBP-2, HER2, and IGF-IR in participants with non-metastatic breast cancer

Clinical Snapshot

Key Findings

• P Value: Not specified for primary outcomes

• Effect Size: Immunogenicity: 70% (150µg), 67% (300µg), 40% (600µg) response rates

• Primary Outcome: All vaccine doses were safe with only grade 1-2 related adverse events

• Nnt Or Sensitivity: 300µg dose selected for Phase II based on sustained 6-month immune responses in 100% of participants

• Confidence Interval: Not reported

Clinical Application

Requires specialised vaccine preparation and immunological monitoring capabilities Would require TGA approval for clinical use. Relevant to Australian breast cancer prevention strategies, potentially complementing existing screening programs. May align with NHMRC research priorities for cancer prevention Patients with non-metastatic breast cancer, particularly those with DCIS or high-risk lesions

Abstract

BACKGROUND: Ductal carcinoma in situ (DCIS) is a preinvasive form of breast cancer. Current treatment consists of surgery, radiation, and often systemic therapy exposing patients to unnecessary health risks. Vaccines targeting DCIS may be a way to intercept preinvasive lesions and prevent the development of invasive breast cancer. METHODS: We developed a Th1 selective multiantigen, polyepitope plasmid-DNA vaccine encoding segments of IGFBP-2, HER2, and IGF-IR, all antigens expressed in hormone receptor positive and negative DCIS. We then performed a Phase I study in participants with non-metastatic breast cancer with no evidence of disease. The primary objective was to assess the safety of 3 monthly intradermal doses (150, 300, or 600 µg) of the tri-antigen vaccine with granulocyte macrophage colony-stimulating factor as an adjuvant. 32 participants were enrolled, 10 per dose level. Toxicity evaluations occurred monthly with vaccination and at 1 and 6 months after the last vaccine. Blood was collected at baseline and at 1 and 6 months after the last immunization to assess cellular immune responses. Participants were followed annually for 5 years for long-term toxicity. RESULTS: There was no significant difference in adverse events (AEs) across dose levels and all related AEs were grades 1 or 2. All doses were immunogenic; responders included 70% of participants at the 150 µg dose level, 67% at the 300 µg dose, and 40% at the 600 µg dose level. All participants at the 300 µg dose retained significant Th1-antigen-specific immune response at 6 months after end of immunizations. T-cells derived from vaccine immunologic responders exhibited gene expression profiles that indicated an increased metabolic fitness as compared with immunologic non-responders. CONCLUSIONS: The tri-antigen vaccine appears safe and immunogenic. The intermediate dose (300 µg) was chosen as the Phase II dose due to the long-term persistence of immunity after vaccination. The vaccine will be studied in Phase II trials for the treatment of DCIS. TRIAL REGISTRATION NUMBER: NCT02780401.

References

1. 1.Stanton, S. E., Cecil, D. L., Bailey, H. H., Liu, Y., Gwin, W. R., Colveler, A. L., Liao, J. B., Wisinski, K. B., Barroilhet, L., Kim, K., Havighurst, T. C., DeShong, K., Twaroski, K., Childs, J. S., Dimond, E., Wojtowicz, M., Heckman-Stoddard, B. M., & Disis, M. L. (2026). Safety and immunogenicity of a tri-antigen vaccine targeting IGFBP-2, HER2, and IGF-IR in participants with non-metastatic breast cancer. Journal for Immunotherapy of Cancer. https://doi.org/10.1136/jitc-2025-014314