Personalized therapy with peptide-based neoantigen vaccine (EVX-01) including a novel adjuvant, CAF®09b, in patients with metastatic melanoma. (31st December 2022)

• Record Type: Journal Article
• Authors: Mørk, Sofie Kirial; Kadivar, Mohammad; Bol, Kalijn Fredrike; Draghi, Arianna; Westergaard, Marie Christine Wulff; Skadborg, Signe Koggersbøl; Overgaard, Nana; Sørensen, Anders Bundgård; Rasmussen, Ida Svahn; Andreasen, Lars Vibe; Yde, Christina Westmose; Trolle, Thomas; Garde, Christian; Friis-Nielsen, Jens; Nørgaard, Nis; Christensen, Dennis; Kringelum, Jens Vindahl; Donia, Marco; Hadrup, Sine Reker; Svane, Inge Marie
• Is Part Of: Oncoimmunology. Volume 11:Number 1(2022)
• Publication Date: 2022-12-31
• Subjects: Personalized therapy -- neoantigen -- immune response -- cancer vaccine -- immunotherapy; Tumors -- Immunological aspects -- Periodicals; Neoplasms -- therapy -- Periodicals; Immunotherapy -- Periodicals; 616.994
• DOI: 10.1080/2162402X.2021.2023255
• Languages: English
• ISSNs: 2162-402X

Abstract

ABSTRACT: 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 PIONEER TM 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 PIONEER TM -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.