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 · 2022 · OncoImmunology
Paper
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.
Analysis
This study investigates the safety, feasibility, and efficacy of EVX-01, a personalized peptide-based neoantigen vaccine combined with a novel adjuvant (CAF®09b) and immune checkpoint inhibitors, in patients with metastatic melanoma.
Discovery
Vladimir Zyrin; Evgeniy Mozheiko; Ivan Valiev; Alexey Lazarev; Tigran Gevorkyan; Matvey Murashko; Konstantin Okonechnikov
Ashling Cannon
Dinghai Zheng; Justin Hong; Jun Wang; Adrien Villain; Mickaël Costallat; Fernando Ulloa Montoya; Vikram Agarwal
Petar Brlek; Jan Kolić; Luka Bulić; Vedrana Škaro; Dragan Primorac
Almohanad A. Alkayyal
Crodel CC; Gork L; Göpel W; Linke P; Sinn K; Miethke J; Hochhaus A; Hilgendorf I
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