EVX-01 Plus Pembrolizumab Elicits Neoantigen-Specific T-Cell Responses in Advanced Melanoma

The personalized, artificial intelligence (AI)–designed peptide vaccine EVX-01 given with pembrolizumab (Keytruda) generated T-cell responses against patient-specific neoantigens and was associated with changes in circulating immune cell populations in patients with advanced melanoma, according to translational data from a phase 2 trial (NCT05309421).¹ The immune findings accompanied durable clinical responses in a population made up predominantly of patients with stage IV disease.

Findings presented at the 2026 SITC Annual Meeting showed that patients enrolled in the single-arm study (n = 16) achieved an objective response rate (ORR) of 75%, including complete responses in 25% and partial responses in 50%. One patient (6%) had stable disease, and 3 patients (19%) had progressive disease as their best response. Responses were assessed by RECIST 1.1 crtieria and confirmed on follow-up scans. Of the 118 vaccine neoantigens tested, 89% induced a T-cell response.

"We showed that EVX-01 induced sustained neoantigen T-cell responses with enrichment of effector memory T cells," presenting author Mads Lausen, PhD, a senior scientist at Evaxion, said in the presentation. "Altogether, these data support the potential of EVX-01 as a cancer vaccine against advanced melanoma."

How was the trial designed?

EVX-01 is an individualized neoantigen vaccine composed of peptides, with the targets for each patient chosen by Evaxion's AI-Immunology platform.

The open-label, single-arm phase 2 trial enrolled patients with stage IV or unresectable stage III melanoma who had not previously received checkpoint inhibitor therapy.

During vaccine production, patients received pembrolizumab at 400 mg intravenously every 6 weeks starting at week 0. Six EVX-01 priming doses were administered every 2 weeks from week 12 through week 22, followed by 4 booster doses at weeks 30, 42, 54, and 78. Patients were followed for 2 years in the main phase. In a 1-year extension phase, 6 patients continued EVX-01 monotherapy, receiving additional doses at weeks 115 and 139, with the trial ending at week 151.

At baseline, 69% of patients were male, 56% were 65 years of age or older, and 94% had an ECOG performance status of 0. Most patients (87.5%) had stage IV disease, and 12.5% had unresectable stage IIIB disease. Half of the patients had BRAF-positive tumors, half had tumor PD-L1 expression above 5%, and 13% had elevated lactate dehydrogenase levels.

What did the immune analyses show?

T-cell reactivity against the pooled EVX-01 neoantigens, measured by interferon-γ ELISpot in in vitro–expanded peripheral blood mononuclear cells, climbed during priming, rose further during boosting, and held steady through the extension phase. The magnitude of responses to individual neoantigens showed a significant positive correlation with AI-Immunology prediction scores (Spearman r = 0.38; P < .001).

Ex vivo flow cytometry of neoantigen-specific T cells from 12 patients showed CD4-positive T-cell responses in 50%, combined CD4-positive and CD8-positive responses in 41.6%, and CD8-positive responses in 8.3%. Lausen noted that the predominance of CD4-positive responses is consistent with findings from other trials of peptide-based neoantigen vaccines.

Compared with nonspecific CD4-positive T cells, neoantigen-specific CD4-positive T cells contained a larger share of cells with effector memory phenotypes, and that share grew over the 2-year study period.

Peripheral immune changes were also observed once EVX-01 priming was complete. Between week 12, when patients had received pembrolizumab alone, and week 30, by which point they had also received 6 doses of EVX-01, the frequency of regulatory T cells fell significantly, whereas the frequency of mature natural killer cells rose significantly.

How durable were the clinical responses?

Among responders, benefit persisted across the 2-year combination period, and patients who continued on EVX-01 alone in the extension phase remained in response for up to 3 years. Evaxion has reported that both clinical and T-cell responses persisted through 3 years of follow-up.² Earlier results from the trial showed durable disease control and T-cell responses with the combination.³

References

1. Lausen M, et al. EVX-01 personalized AI-designed vaccine plus pembrolizumab induce neoantigen-specific T-cell responses and systemic immune modulation in advanced melanoma. Paper presented at: 2026 Society for Immunotherapy of Cancer Annual Meeting; November 4-8, 2026; Phoenix, AZ. Abstract 502
2. Evaxion to present broad biomarker data from phase 2 trial with personalized cancer vaccine EVX-01 at the SITC 2026 Annual Meeting. News release. Evaxion A/S. November 3, 2026. Accessed November 6, 2026. https://www.biospace.com/press-releases/evaxion-to-present-broad-biomarker-data-from-phase-2-trial-with-personalized-cancer-vaccine-evx-01-at-the-sitc-2026-annual-meeting
3. Khattak A, Ascierto P, Cimminiello C, et al. EVX-01, a personalized cancer vaccine, induces potent T-cell responses and durable disease control in advanced melanoma: 2-year follow-up. Presented at: 2025 ESMO Congress; October 17-21, 2025; Berlin, Germany. Abstract 1516MO.