{
  "abstract": "Background Immune checkpoint Inhibitor (ICI) therapy has revolutionized the treatment of advanced melanoma. However, a fraction of patients do not benefit from the treatment, highlighting the need to better understand the factors that determine therapeutic success. Cancer vaccines targeting neoantigens (NeoAgs) derived from tumor-specific mutations have emerged as novel and promising treatment modality. Early clinical studies across multiple indications have demonstrated a tolerable safety profile and provided growing evidence of clinical benefit. The personalized NeoAg cancer vaccine EVX-01 is evaluated in combination with Pembrolizumab in a phase 2 trial in advanced melanoma ( NCT05309421), with 80% of the vaccine targets eliciting T-cell responses and an objective response rate of 68.8% in the overall cohort. To identify potential biomarkers underlying vaccine immunogenicity and clinical benefit, we applied immune assays and characterized the immune responses elicited by the treatment in detail.Methods Evaxion’s target discovery AI-Immunology™ platform was used to identify and rank patient-specific NeoAgs, selecting up to 10 targets per patient for the vaccine. 16 patients with stage III/IV unresectable melanoma received Pembrolizumab and, 12 weeks later, treatment with six initial EVX-01 priming and three booster vaccinations. Longitudinal blood samples were collected before, during, and after treatment and processed to peripheral blood mononuclear cells (PBMCs) for immune and exploratory biomarker analyses. Vaccine NeoAg-specific T cells were assessed by IFNγ ELISpot, and their functional phenotype was characterized by activation marker and intracellular cytokine staining, followed by 18-colour Spectral Flow Cytometry analysis. Treatment-induced changes of a broad selection of immune cell subsets in PBMCs were monitored using a 25-colour Spectral Flow Cytometry immunophenotyping panel.Results Vaccine priming led to strong vaccine-specific T-cell responses in all evaluable patients (n=15), while repeated booster immunizations amplified the magnitude, broadness, and durability of the responses. Vaccine-specific responses were mediated by cytokine-producing CD4+ and CD8+ T cells. Longitudinal profiling of vaccine-specific T cells for expression of activation, exhaustion, memory, and cytotoxicity markers and deep characterization of functionally diverse immune cell subsets are ongoing and may assist in the identification of pharmacodynamic biomarkers that correlate with clinical response.Conclusions The personalized cancer vaccine EVX-01 induces strong and durable immune responses driven by reactive CD4+ and CD8+ T cells. Ongoing immune and biomarker analyses may increase our understanding of how the therapy shapes anti-tumor immunity and assist in identifying predictive biomarkers that may guide treatment decisions in the future.",
  "authors": [
    {
      "affiliations": [
        "Technical University of Denmark, Kongens Lyngby, Zealand, Denmark",
        "Evaxion A/S, Hørsholm, Zealand, Denmark"
      ],
      "name": "Michail A Pavlidis"
    },
    {
      "affiliations": [
        "Evaxion A/S, Hørsholm, Zealand, Denmark"
      ],
      "name": "Mads Lausen"
    },
    {
      "affiliations": [
        "Evaxion A/S, Hørsholm, Zealand, Denmark"
      ],
      "name": "Rasmus O Andersen"
    },
    {
      "affiliations": [
        "Evaxion A/S, Hørsholm, Zealand, Denmark"
      ],
      "name": "Nadia Viborg"
    },
    {
      "affiliations": [
        "Evaxion A/S, Hørsholm, Zealand, Denmark"
      ],
      "name": "Nikolas H Thuesen"
    },
    {
      "affiliations": [
        "Melanoma Institute Australia, The University of Sydney, Sydney, NSW, Australia"
      ],
      "name": "Georgina Long"
    },
    {
      "affiliations": [
        "Hollywood Private Hospital and Edith Cowan University, Perth, WA, Australia"
      ],
      "name": "Adnan Khattak"
    },
    {
      "affiliations": [
        "Istituto Nazionale Tumori IRCCS Fondazione G. Pascale, Naples, Italy"
      ],
      "name": "Paolo Ascierto"
    },
    {
      "affiliations": [
        "Divisione di Oncologia Medica del Melanoma, Sarcoma e Tumori Rari, IEO – Istituto Europeo di Oncologia IRCCS, Milan, Lombardy, Italy"
      ],
      "name": "Carolina Cimminiello"
    },
    {
      "affiliations": [
        "Merck and Co., Inc., Rahway, NJ, USA"
      ],
      "name": "Michael J Chisamore"
    },
    {
      "affiliations": [
        "Evaxion A/S, Hørsholm, Zealand, Denmark"
      ],
      "name": "Thomas S Jepsen"
    },
    {
      "affiliations": [
        "Evaxion A/S, Hørsholm, Zealand, Denmark"
      ],
      "name": "Birgitte Rønø"
    },
    {
      "affiliations": [
        "Evaxion A/S, Hørsholm, Zealand, Denmark"
      ],
      "name": "Stine F Thorsen"
    },
    {
      "affiliations": [
        "Evaxion A/S, Hørsholm, Zealand, Denmark"
      ],
      "name": "Thomas Trolle"
    },
    {
      "affiliations": [
        "Evaxion A/S, Hørsholm, Zealand, Denmark"
      ],
      "name": "Benjamin Wolthers"
    },
    {
      "affiliations": [
        "Technical University of Denmark, Kongens Lyngby, Zealand, Denmark"
      ],
      "name": "Sunil K Saini"
    },
    {
      "affiliations": [
        "Evaxion A/S, Hørsholm, Zealand, Denmark"
      ],
      "name": "Daniela Kleine-Kohlbrecher"
    }
  ],
  "title": "605 Immune correlates of clinical response following treatment with the personalized cancer vaccine EVX-01 and pembrolizumab in advanced melanoma patients",
  "uid": "eb600d46-50d4-5da3-80e1-980e5a0bc126"
}