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546 A phase I dose escalation study of STEMVAC, a multi-antigen, multi-epitope Th1 selective plasmid-based vaccine, targeting stem cell associated proteins in patients with advanced breast cancer
  1. Mary Disis1,
  2. Ying Liu1,
  3. Sasha Stanton2,
  4. William Gwin1,
  5. Andrew Coveler1,
  6. John Liao1,
  7. Jennifer Childs1 and
  8. Denise Cecil1
  1. 1UW Medicine Cancer Vaccine Institute, Seattle, WA, United States
  2. 2Providence, Portland, OR, United States


Background Cancer stem cell or epithelial/mesenchymal transition antigens could have utility in vaccines for cancer treatment and prevention. We identified class II binding T-cell epitopes from non-mutated tumor antigens that selectively elicit a Th1 response. We constructed a 5 antigen (CD105-Yb-1-SOX2-CDH3-MDM2) multi-epitope plasmid-based vaccine; STEMVAC, and conducted a Phase I dose escalation study in patients with advanced breast cancer.

Methods Patients with advanced HER2 negative breast cancer previously treated and in remission were sequentially enrolled to 3 dose arms: 150, 300, or 600mcg of STEMVAC. Vaccines were given monthly intradermally for three doses with rhu-GM-CSF (100mcg) as adjuvant. Two booster immunizations (same dose) were given 3 and 6 months after the third vaccine. Primary endpoints were safety and immunogenicity. Secondary endpoints included persistence of the immune response after vaccination and assessment of potential stimulation of T-regulatory (Treg) cells or myeloid derived suppressor cells (MDSC) to the overexpressed non-mutated antigens expressed in STEMVAC. Antigen specific immunity was measured by IFN-gamma (g) and IL-10 ELISPOT. Immune cells were evaluated by flow cytometry.

Results Seventy-five percent of patients were hormone receptor positive and 25% triple negative (TNBC). Patient characteristics, including breast cancer subtype, did not vary significantly between doses (all p>0.1). The vast majority of adverse events (AE), 98%, were grades 1/2. The most common AE were injection site reactions, flu-like syndrome, and transient leukopenia and lymphopenia. Arm 1 (150mcg) generated transient low levels of IFN-g secreting T-cells to a median of 1 antigen per patient and considered the least immunogenic dose. Arm 2 (300mcg) resulted in a mean response (sum of all antigens) of 1 antigen specific T-cell per 2500 (1:2500) PBMC at week 16 (p<0.05 compared to baseline) which boosted to 1:1500 by week 60 (p<0.001 compared to baseline). Immune responses for Arm 3 (600mcg) were statistically similar to Arm 2 at 16 weeks, but did not persist and could not be boosted. In Arm 2, booster immunizations increased the incidence and breadth of the immune response, with patients showing significant IFN-g secretion to a median of 4/5 antigens. At 16 weeks, there was no increase in antigen specific IL-10 secreting T-cells, Treg, or MDSC at any dose.

Conclusions STEMVAC selectively elicits high level persistent Type I T-cell responses at the 300mcg dose. Two Phase II studies are enrolling; adjuvant setting for TNBC (NCT05455658) and maintenance therapy with pembrolizumab in metastatic non-small cell lung cancer (NCT05242965).

Acknowledgements This work was supported by the Department of Defence Breast Cancer Program, VGG, and the Breast Cancer Allliance. We thank all our patient particpants-we could not have completed this study without them.

Trial Registration NCT02157051

Ethics Approval The study was approved by the Fred Hutchinson Cancer Research Center Institutional Review Board (#7396). All partcipants gave written informed consent before partcipation in the study.

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