{
  "abstract": "Background VP-315 is an intratumorally injected oncolytic peptide in development as a non-surgical immunotherapeutic agent as a potential first line therapy in a primary or neoadjuvant setting for patients with BCC. 1 After intratumoral injection, VP-315 enters BCC cells by perturbing plasma membranes and targets mitochondria, and other organelles, causing cell death and release of danger signals (DAMPs) and a broad repertoire of tumor specific antigens.2 3 The primary objective of this exploratory analysis was to evaluate the immune response to VP-315 treatment in the tumor microenvironment (TME) in a subset of subjects/BCC tumors (N=22/24) that were enrolled in Part 2 of a Phase 2 multi-center, proof-of-concept study designed to assess the safety, tolerability, maximum tolerated dose, and objective antitumor efficacy of once daily dosing (2 or 3 days) of 8 mg of VP-315 in up to 2 target lesions per subject4–6 (NCT05188729).Methods Multiplexed immunofluorescence immunohistochemistry was performed on slices from tumor tissue biopsies collected pre-treatment and at 12-14-weeks post-treatment. Slices were stained for T-cell subsets (CD3+, CD4+, CD8+), macrophage (CD68+), B-cells (CD20+), as well as for immunosuppressive cells expressing the FoxP3+ and PD-L1+ markers. Calculation of densities (cells/mm 2) of cells expressing the individual markers, as well as specific phenotypes from combinations of the markers, was performed by quantification of fluorescent microscopic images.Results VP-315 treatment reprograms the TME as evidenced by clinically meaningful and statistically significant increases in the densities of CD3+, CD3+/CD4+ helper cells and CD3+/CD8 cytotoxic T-cells (p<0.05; pre- vs post-treatment) and increased B-cell infiltration (CD20+) in the tumor region. Furthermore, there was a reduction of immunosuppression in the TME after treatment with a decrease in the CD68+/PD-L1+ macrophage population in the overall tumor region and significant decreases in immunosuppressive CD3+/CD4+/PD-L1 T-Helper Cells (p<0.01), CD3+/CD8+/PD-L1 cytotoxic T-Cells (p<0.05), and CD68+/PD-L1 M1-like Macrophage (p≤0.001) in the peritumoral region within 75 µm of the pre-treatment tumor margin.Conclusions VP-315 treatment induced a robust immune response with both cell-mediated and humoral components in the TME suggesting a reset of the immune switch toward anti-tumor immunity. VP-315 is a promising treatment for non-surgical first line BCC therapy in a primary or neoadjuvant setting and this data supports the clinical efficacy and histological clearance observations previously reported.Acknowledgements LTX-315 is being studied as VP-315 in BCC.Trial Registration NCT05188729References Sveinbjørnsson B, Camilio KA, Haug BE, Rekdal Ø. LTX-315: a first-in-class oncolytic peptide that reprograms the tumor microenvironment . Future Med Chem. 2017;9(12):1339–1344.Eike LM, Yang N, Rekdal Ø, Sveinbjørnsson B. The oncolytic peptide LTX-315 induces cell death and DAMP release by mitochondria distortion in human melanoma cells. Oncotarget. 2015 Oct 27;6(33):34910–23.Camilio KA, Berge G, Ravuri CS, Rekdal O, Sveinbjørnsson B. Complete regression and systemic protective immune responses obtained in B16 melanomas after treatment with LTX-315. Cancer Immunol Immunother. 2014;63(6):601–613.Results of a phase 2 multicenter study evaluating the safety and tolerability of VP-315, an investigational therapy for basal cell carcinoma. J of Skin. 2024;8(6):s480. doi:10.25251/skin.8.supp.480Results of a phase 2 multicenter study to evaluate the efficacy of VP-315, an investigational therapy for basal cell carcinoma. J of Skin. 2024;8(6):s481. doi:10.25251/skin.8.supp.481The calculated objective response rate (ORR) of 97% from post-hoc analysis of a phase 2 multicenter study to evaluate the efficacy of VP-315, an investigational therapy for basal cell carcinoma (BCC): (ORR) of 97% from post-hoc analysis of a phase 2 to evaluate the efficacy of VP-315, an investigational therapy for basal cell carcinoma (BCC). J of Skin. 2025;9(2):s565. doi:10.25251/skin.10.supp.565Ethics Approval This study was approved by Advarra Institutional Review Board; protocol number Pro00058474.Consent Written informed consent was obtained from the patient for publication of this abstract and any accompanying images. A copy of the written consent is available for review by the Editor of this journal.",
  "authors": [
    {
      "affiliations": [
        "Moffitt Cancer Center, Tampa, FL, USA"
      ],
      "name": "Kenneth Y Tsai"
    },
    {
      "affiliations": [
        "PBM Capital Group, Charlottesville, VA, USA"
      ],
      "name": "David K Glover"
    },
    {
      "affiliations": [
        "Therapeutics Clinical Research, San Diego, CA, USA"
      ],
      "name": "Neal Bhatia"
    },
    {
      "affiliations": [
        "Georgia Dermatology Partners and Gwinnett Clinical Research Center Inc., Snellville, GA, USA"
      ],
      "name": "Jonathan S Weiss"
    },
    {
      "affiliations": [
        "Austin Institute for Clinical Research, Houston, TX, USA"
      ],
      "name": "Megan Couvillion"
    },
    {
      "affiliations": [
        "Austin Institute for Clinical Research, Pflugerville, TX, USA"
      ],
      "name": "Edward Lain"
    },
    {
      "affiliations": [
        "Austin Institute for Clinical Research, Dripping Springs, TX, USA"
      ],
      "name": "Daniel Carrasco"
    },
    {
      "affiliations": [
        "US Dermatology Partners, Rockville, MD, USA"
      ],
      "name": "Benjamin Lockshin"
    },
    {
      "affiliations": [
        "Allcutis Research LLC, Portsmouth, NH, USA"
      ],
      "name": "Abel Jarell"
    },
    {
      "affiliations": [
        "University of North Carolina, Chapel Hill, NC, USA",
        "Formerly of University of Pittsburgh, Pittsburgh, PA, USA"
      ],
      "name": "Laura Ferris"
    },
    {
      "affiliations": [
        "The University of Illinois at Chicago and Jesse Brown VA Medical Center, Chicago, IL, USA",
        "Franklin University of Medicine and Science/The Chicago Medical School, North Chicago, IL, USA"
      ],
      "name": "Rania Agha"
    },
    {
      "affiliations": [
        "Verrica Pharmaceuticals Inc., West Chester, PA, USA"
      ],
      "name": "Cynthia Willson"
    },
    {
      "affiliations": [
        "Verrica Pharmaceuticals Inc., West Chester, PA, USA"
      ],
      "name": "Thomas F Haws"
    },
    {
      "affiliations": [
        "Verrica Pharmaceuticals Inc., West Chester, PA, USA"
      ],
      "name": "Jayson Rieger"
    },
    {
      "affiliations": [
        "Verrica Pharmaceuticals Inc., West Chester, PA, USA"
      ],
      "name": "Pamela J Rumney"
    },
    {
      "affiliations": [
        "Verrica Pharmaceuticals Inc., West Chester, PA, USA"
      ],
      "name": "Susan RS Cutler"
    },
    {
      "affiliations": [
        "Icahn School of Medicine at Mount Sinai Hospital, New York, NY, USA",
        "Formerly of Verrica Pharmaceuticals Inc., West Chester, PA, USA"
      ],
      "name": "Gary Goldenberg"
    },
    {
      "affiliations": [
        "Verrica Pharmaceuticals Inc., West Chester, PA, USA"
      ],
      "name": "Noah Rosenberg"
    }
  ],
  "title": "529 Exploratory analysis of a phase 2 multicenter study evaluating local immune activation in the tumor microenvironment 12 weeks post VP-315, an investigational therapy for basal cell carcinoma (BCC)",
  "uid": "14954dbf-1c23-55f9-adc5-96bd09c3e50b"
}