Dose escalation study of a personalized peptide-based neoantigen vaccine (EVX-01) in patients with metastatic melanoma

Sofie Kirial Mørk*, Signe Koggersbøl Skadborg, Benedetta Albieri, Arianna Draghi, Kalijn Bol, Mohammad Kadivar, Marie Christine Wulff Westergaard, Joachim Stoltenborg Granhøj, Annie Borch, Nadia Viborg Petersen, Nikolas Thuesen, Ida Svahn Rasmussen, Lars Vibe Andreasen, Rebecca Bach Dohn, Christina Westmose Yde, Nis Noergaard, Torben Lorentzen, Anders Bundgaard Soerensen, Daniela Kleine-Kohlbrecher, Anders JespersenDennis Christensen, Jens Kringelum, Marco Donia, Sine Reker Hadrup, Inge Marie Svane

*Corresponding author for this work

Research output: Contribution to journalJournal articleResearchpeer-review

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Background  Neoantigens can serve as targets for T cell-mediated antitumor immunity via personalized neopeptide vaccines. Interim data from our clinical study NCT03715985 showed that the personalized peptide-based neoantigen vaccine EVX-01, formulated in the liposomal adjuvant, CAF09b, was safe and able to elicit EVX-01-specific T cell responses in patients with metastatic melanoma. Here, we present results from the dose-escalation part of the study, evaluating the feasibility, safety, efficacy, and immunogenicity of EVX-01 in addition to anti-PD-1 therapy. 

Methods  Patients with metastatic melanoma on anti-PD-1 therapy were treated in three cohorts with increasing vaccine dosages (twofold and fourfold). Tumor-derived neoantigens were selected by the AI platform PIONEER and used in personalized therapeutic cancer peptide vaccines EVX-01. Vaccines were administered at 2-week intervals for a total of three intraperitoneal and three intramuscular injections. The study's primary endpoint was safety and tolerability. Additional endpoints were immunological responses, survival, and objective response rates. 

Results  Compared with the base dose level previously reported, no new vaccine-related serious adverse events were observed during dose escalation of EVX-01 in combination with an anti-PD-1 agent given according to local guidelines. Two patients at the third dose level (fourfold dose) developed grade 3 toxicity, most likely related to pembrolizumab. Overall, 8 out of the 12 patients had objective clinical responses (6 partial response (PR) and 2 CR), with all 4 patients at the highest dose level having a CR (1 CR, 3 PR). EVX-01 induced peptide-specific CD4+ and/or CD8+T cell responses in all treated patients, with CD4+T cells as the dominating responses. The magnitude of immune responses measured by IFN-γELISpot assay correlated with individual peptide doses. A significant correlation between the PIONEER quality score and induced T cell immunogenicity was detected, while better CRs correlated with both the number of immunogenic EVX-01 peptides and the PIONEER quality score. 

Conclusion  Immunization with EVX-01-CAF09b in addition to anti-PD-1 therapy was shown to be safe and well tolerated and elicit vaccine neoantigen-specific CD4+and CD8+ T cell responses at all dose levels. In addition, objective tumor responses were observed in 67% of patients. The results encourage further assessment of the antitumor efficacy of EVX-01 in combination with anti-PD-1 therapy.

Original languageEnglish
Article numbere008817
JournalJournal for ImmunoTherapy of Cancer
Issue number5
Number of pages16
Publication statusPublished - 2024


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