Abstract Early Results from a Phase 1 Clinical Trial of a Cancer Vaccine Targeting Tumor Associated Antigen MUC1 for Immune Interception of Breast Cancer in Patients with Ductal Carcinoma in SituIntroductionHypoglycosylated tumor MUC1, a transmembrane glycoprotein, is recognized by human T-cells and antibodies as a tumor-associated antigen. It is overexpressed in premalignant precursor lesions, including ductal carcinoma in situ (DCIS), thereby serving as a potential potent DCIS rejection target. Vaccine-induced immune response to MUC1 may halt DCIS recurrence or progression to invasive disease and may offer a future strategy for primary disease prevention in high-risk individuals. We hypothesize that our MUC1 peptide vaccine will be both safe and immunogenic in patients with DCIS and that the elicited systemic immune response will affect changes in the microenvironment of the DCIS from pro- to anti-tumor. MethodsThis single institution, open label, randomized phase I clinical trial (NCT06218303) is designed for 50 post-menopausal women with previously untreated estrogen-receptor positive DCIS histologically confirmed on core needle biopsy (CNB). Patients with autoimmune diseases were excluded. Patients are randomized 2:1 to the vaccine group. The vaccine is composed of a 100aa long MUC1 peptide corresponding to 5 tandem repeats of 20 amino acids from the MUC1 variable number of tandem repeats region (VNTR), admixed with the poly-ICLC adjuvant Hiltonol. The vaccine is administered subcutaneously (SC) or intramuscularly (IM). The vaccine group receives the MUC1 peptide vaccine series pre-operatively (at 0, 2, and 10 weeks) with an optional aromatase inhibitor (AI). The control group receives only optional AI. All undergo surgery at 12 weeks. Research blood is drawn in the vaccine group at baseline and 2 weeks after each vaccine, and in the control group at baseline and at week 12. Tissue from the pre-treatment CNB and the post-treatment operation are also collected. An optional booster is available to vaccine responders 6 months post-surgery.The primary endpoint is vaccine immunogenicity, measured as anti-MUC1 IgG level. Vaccine responders are identified based on a 2-fold increase in serum anti-MUC1 IgG from baseline, using enzyme-linked immunosorbent assay (ELISA). Adverse events are monitored per Common Terminology Criteria for Adverse Events (CTCAE) version 5.0.Fisher’s exact test will compare primary immunogenicity between the study arms with one-sided α = 0.05. Correlative studies include extensive phenotyping of circulating as well as DCIS-infiltrating immune cells and increases in anti-MUC1 cellular immunity post vaccination. ResultsTo date,13 patients completed the study: 7 in the vaccine and 6 in the control group. Mean age is 66 years. There were no serious adverse events. The primary vaccine series elicited or boosted anti-MUC1 IgG in 6 of 7 vaccinated women, for a response rate of 86%. Only 1 patient to date was eligible to receive the booster vaccine and showed a strong immune memory response. There was no anti-MUC1 IgG present in the control group. Extensive phenotyping of peripheral blood mononuclear cell samples from both groups and evaluation of MUC-specific cellular responses are in progress, as are tissue analyses. ConclusionMUC1 peptide vaccine given in the premalignant DCIS setting is safe in the first 7 patients to receive the vaccine. The 86% immune response rate predicts a high rate of response, which will allow us to study immune mechanisms activated by the vaccine, including changes in the DCIS microenvironment. Citation Format: E. J. Diego, J. A. Foldi, P. F. McAuliffe, Q. Sabih, L. A. Emens, A. Salazar, O. J. Finn. Early Results from a Phase 1 Clinical Study of a Cancer Vaccine Targeting Tumor Associated Antigen MUC1 in Ductal Carcinoma in Situ for Immune Interception of Breast Cancer abstract. In: Proceedings of the San Antonio Breast Cancer Symposium 2025; 2025 Dec 9-12; San Antonio, TX. Philadelphia (PA): AACR; Clin Cancer Res 2026;32(4 Suppl):Abstract nr PS4-06-18.
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