A clinical study of a prototype DAA/TAA vaccine targeting MUC1 for immune interception and prevention in ductal carcinoma in situ.

Abstract

TPS2699 Background: Hypoglycosylated tumor MUC1 is a transmembrane glycoprotein, 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), serving as a potential potent DCIS rejection target. Vaccine-induced immune response to MUC1 may halt DCIS recurrence or progression to invasive disease and offer a future strategy for disease prevention in high-risk individuals. The hypothesis is MUC1 peptide vaccine is safe and immunogenic in patients with DCIS and the elicited systemic immune response will affect changes in the microenvironment of the DCIS from pro- to anti-tumor. Eligibility: Female, 18 years or older with biopsy proven ER+ DCIS with surgery planned as part of definite local therapy. Design: This single institution, open label, randomized phase I clinical trial (NCT06218303) is seeking 50 women with untreated ER+ DCIS confirmed on core needle biopsy (CNB). 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 group receives the MUC1 peptide vaccine series pre-op (at 0, 2, and 10 weeks) with optional tamoxifen or an aromatase inhibitor (AI). The control group receives only optional tamoxifen or AI. All have 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 surgery are collected. An optional booster is available to vaccine responders 6 months post-surgery. Aims: The primary objective is to assess the immunogenicity of the MUC1 vaccine in ER+ DCIS patients prior to surgery. The secondary objective is to assess the safety and feasibility of the MUC1 vaccine in ER+ DCIS patients prior to surgery. The exploratory objective is to characterize peripheral MUC1-specific effector T-cells, regulatory T-cells and myeloid-derived suppressor cells (MDSC) at baseline and after vaccination. Changes in features of the tumor microenvironment and peripheral immunity at baseline and after vaccination may also be explored. Methods: Sample size/power: Assuming a one-sided type I error α ≤ 0.05 and the rate of patients having a ≥ 2× change in anti-MUC1 IgG 1 is 35% in the vaccine arm and 2% in the control arm, a sample sizes of n=32 and 18 respectively in each arm will yield 88% power. With a dropout of up to 3 patients in each arm, the remaining sample size will still yield power of 82%. Statistical analysis: Fisher’s exact test will be performed at the one-sided α=0.05 for the primary immunogenicity endpoint for comparing the experimental arm to the control arm. Clinical trial information: NCT06218303 .