Immunogenicity of an AI-designed personalized neoantigen vaccine, EVX-01, in combination with anti-PD-1 therapy in patients with metastatic melanoma.
Authors: Lausen Mads , Petersen Nadia Viborg , Long Georgina V. , Khattak Muhammad Adnan , Ascierto Paolo Antonio , Queirolo Paola , Pavlidis Michail Angelos , Friis Thorsen Stine , Chisamore Michael Jon , Kleine-Kohlbrecher Daniela , Trolle Thomas , Rønø Birgitte 
Published: July 2024

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Background: Personalized vaccines, targeting mutation-derived neoantigens (neoAg), represent a promising frontier in cancer immunotherapy. Here, we characterize the vaccine-induced immune response in seven melanoma patients treated with the AI-generated personalized cancer vaccine, EVX-01, in the ongoing single arm multicenter trial (NCT05309421). Data from an additional five patients will be available at the time of presentation. Methods: Tumor-specific neoAgs were identified and selected using the proprietary vaccine target discovery AI-Immunology platform based on tumor DNA- and RNA-sequencing data. The top-ranked neoAgs for each patient were manufactured as synthetic long peptides and formulated with an adjuvant, creating the personalized cancer vaccine, EVX-01, tailored to the individual tumor and immune system characteristics. Patients initiated anti-PD1 therapy (Pembrolizumab) 12 weeks prior to EVX-01 administration. Each patient received six priming doses of EVX-01 administered bi-weekly and will be followed by four booster immunizations at later timepoints. Peripheral blood mononuclear cells (PBMCs) were isolated from blood samples collected at different timepoints to evaluate the effect of anti-PD1 therapy, EVX-01 priming immunizations and EVX-01 booster immunizations on T-cell immunogenicity. NeoAg-specific T-cell responses were evaluated by IFN-γ ELISpot assay and intracellular cytokine staining after T cell in vitro expansion with vaccine neoAgs. Results: Immunogenicity analysis of PBMC samples from seven patients demonstrated that EVX-01 induced neoAg-specific immune responses in all patients after the priming phase. The effect of booster immunizations on neoAg-specific T-cell responses was analyzed in the patients who had reached these late visits of the study, and it demonstrated a clear trend towards increased immune responses after the first booster dose. The observed responses were mediated by both CD4+ and CD8+ neoAg-specific T-cells. Investigations of the response induced by the individual vaccine neoAgs revealed that the majority of the EVX-01 neoAgs triggered a specific T-cell response, affirming the ability of the AI-Immunology™ platform to precisely select effective vaccine targets. Data from an additional five patients will be available at the time of presentation. Importantly EVX-01 was safe and well-tolerated, with only grade 1 and 2 ADRs related to EVX-01 even after boosting. The combination of EVX-01 and anti-PD1 also appeared safe and well tolerated. Conclusions: EVX-01 induced neoAg-specific immune responses in all analyzed patients and a broad response against the neoAgs. These results further validate the precision and predictive power of our proprietary vaccine target discovery AI-Immunology platform. The combination of EVX-01 and anti-PD1 was safe and well tolerated. Clinical trial information: NCT05309421 .