OncoImmunology (Dec 2022)

Personalized therapy with peptide-based neoantigen vaccine (EVX-01) including a novel adjuvant, CAF®09b, in patients with metastatic melanoma

  • Sofie Kirial Mørk,
  • Mohammad Kadivar,
  • Kalijn Fredrike Bol,
  • Arianna Draghi,
  • Marie Christine Wulff Westergaard,
  • Signe Koggersbøl Skadborg,
  • Nana Overgaard,
  • Anders Bundgård Sørensen,
  • Ida Svahn Rasmussen,
  • Lars Vibe Andreasen,
  • Christina Westmose Yde,
  • Thomas Trolle,
  • Christian Garde,
  • Jens Friis-Nielsen,
  • Nis Nørgaard,
  • Dennis Christensen,
  • Jens Vindahl Kringelum,
  • Marco Donia,
  • Sine Reker Hadrup,
  • Inge Marie Svane

DOI
https://doi.org/10.1080/2162402X.2021.2023255
Journal volume & issue
Vol. 11, no. 1

Abstract

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The majority of neoantigens arise from unique mutations that are not shared between individual patients, making neoantigen-directed immunotherapy a fully personalized treatment approach. Novel technical advances in next-generation sequencing of tumor samples and artificial intelligence (AI) allow fast and systematic prediction of tumor neoantigens. This study investigates feasibility, safety, immunity, and anti-tumor potential of the personalized peptide-based neoantigen vaccine, EVX-01, including the novel CD8+ T-cell inducing adjuvant, CAF®09b, in patients with metastatic melanoma (NTC03715985). The AI platform PIONEERTM was used for identification of tumor-derived neoantigens to be included in a peptide-based personalized therapeutic cancer vaccine. EVX-01 immunotherapy consisted of 6 administrations with 5–10 PIONEERTM-predicted neoantigens as synthetic peptides combined with the novel liposome-based Cationic Adjuvant Formulation 09b (CAF®09b) to strengthen T-cell responses. EVX-01 was combined with immune checkpoint inhibitors to augment the activity of EVX-01-induced immune responses. The primary endpoint was safety, exploratory endpoints included feasibility, immunologic and objective responses. This interim analysis reports the results from the first dose-level cohort of five patients. We documented a short vaccine manufacturing time of 48–55 days which enabled the initiation of EVX-01 treatment within 60 days from baseline biopsy. No severe adverse events were observed. EVX-01 elicited long-lasting EVX-01-specific T-cell responses in all patients. Competitive manufacturing time was demonstrated. EVX-01 was shown to be safe and able to elicit immune responses targeting tumor neoantigens with encouraging early indications of a clinical and meaningful antitumor efficacy, warranting further study.

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