TY - JOUR

T1 - Personalized therapy with peptide-based neoantigen vaccine (EVX-01) including a novel adjuvant, CAF®09b, in patients with metastatic melanoma

AU - Mork, Sofie Kirial

AU - Kadivar, Mohammad

AU - Bol, Kalijn Fredrike

AU - Draghi, Arianna

AU - Westergaard, Marie Christine Wulff

AU - Skadborg, Signe Koggersbol

AU - Overgaard, Nana

AU - Sorensen, Anders Bundgard

AU - Rasmussen, Ida Svahn

AU - Andreasen, Lars Vibe

AU - Yde, Christina Westmose

AU - Trolle, Thomas

AU - Garde, Christian

AU - Friis-Nielsen, Jens

AU - Norgaard, Nis

AU - Christensen, Dennis

AU - Kringelum, Jens Vindahl

AU - Donia, Marco

AU - Hadrup, Sine Reker

AU - Svane, Inge Marie

PY - 2022/12/31

Y1 - 2022/12/31

N2 - 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 (R) 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 (R) 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.

AB - 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 (R) 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 (R) 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.

KW - Personalized therapy

KW - neoantigen

KW - immune response

KW - cancer vaccine

KW - immunotherapy

KW - T-CELL RESPONSES

KW - CANCER

KW - CAF09

KW - ANTI-PD-1

KW - BLOCKADE

KW - IMMUNITY

KW - AVIDITY

KW - FUTURE

U2 - 10.1080/2162402X.2021.2023255

DO - 10.1080/2162402X.2021.2023255

M3 - Journal article

C2 - 35036074

VL - 11

JO - OncoImmunology

JF - OncoImmunology

SN - 2162-4011

IS - 1

M1 - 2023255

ER -