EVX-01 melanoma trial reports 75% response rate and T-cell activity

By Daniel Okafor

Twelve of 16 patients with advanced melanoma achieved an objective response in a phase 2 trial of the personalized vaccine EVX-01 plus pembrolizumab.

The 75% objective response rate came from an open-label, single-arm study, which cannot isolate EVX-01’s contribution from pembrolizumab. The cohort included mostly patients with stage IV disease.

Translational results from trial NCT05309421 were presented as abstract 502 at the 2026 Society for Immunotherapy of Cancer Annual Meeting in Phoenix, Arizona, Nov. 4-8. Evaxion had issued a preview of the data on Nov. 3.

What did the phase 2 trial show?

Among 16 participants, the objective response rate reached 75%. Best responses broke down as follows:

• Complete response: 25% of patients
• Partial response: 50%
• Stable disease: one patient, or 6%
• Progressive disease: three patients, or 19%

Investigators assessed responses under RECIST 1.1 criteria and confirmed them on follow-up scans. The objective response rate combined complete and partial responses.

Of the 118 patient-specific vaccine neoantigens tested, 89% induced a T-cell response. The immune findings accompanied the clinical activity in a predominantly stage IV population.

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

Takeaway: The response and immune findings move in the same direction, but the small, uncontrolled cohort cannot establish the vaccine’s independent benefit.

How was the vaccine and immunotherapy given?

EVX-01 was an individualized neoantigen vaccine composed of peptides. Evaxion’s AI-Immunology platform selected the targets for each patient.

The trial enrolled patients with stage IV or unresectable stage III melanoma who had not previously received checkpoint inhibitor therapy. Its schedule began with pembrolizumab and added vaccination 12 weeks later.

• Pembrolizumab: 400 mg intravenously every six weeks, starting at week 0 during vaccine production
• Priming: Six EVX-01 doses every two weeks from week 12 through week 22
• Boosting: Four EVX-01 doses at weeks 30, 42, 54, and 78
• Follow-up: Two years in the main phase, followed by a one-year extension
• Extension treatment: Six patients continued on EVX-01 monotherapy, receiving doses at weeks 115 and 139; the trial ended at week 151

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

Takeaway: The schedule tested vaccination after checkpoint blockade began, then continued antigen-specific dosing through the combination phase.

What did the immune analyses show?

Pooled EVX-01 neoantigen reactivity climbed during priming and rose further during boosting. It then held steady through the extension phase. Investigators measured this activity with interferon-γ ELISpot in peripheral blood mononuclear cells expanded in vitro.

The magnitude of responses to individual neoantigens correlated positively with AI-Immunology prediction scores. The association reached statistical significance, with a Spearman correlation of 0.38 and P < .001.

Ex vivo flow cytometry in 12 patients found:

• CD4-positive T-cell responses in 50%
• Combined CD4-positive and CD8-positive responses in 41.6%
• CD8-positive responses in 8.3%

Lausen said the predominance of CD4-positive responses was 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. That share increased over the two-year study period.

The researchers also documented changes in circulating immune populations after priming. Between week 12, when patients had received pembrolizumab alone, and week 30, after six EVX-01 doses, regulatory T-cell frequency fell significantly. Mature natural killer cell frequency rose significantly over the same interval.

Takeaway: EVX-01 generated measurable patient-specific immunity and shifted circulating immune-cell populations.

How durable were the responses?

Among patients who responded, benefit persisted throughout the two-year EVX-01 and pembrolizumab combination period. Six patients then continued on EVX-01 alone during the extension phase, where responses persisted for up to three years.

Evaxion has separately reported that both clinical and T-cell responses continued through three years of follow-up. That statement reflects company-reported extension data rather than a randomized estimate of the vaccine’s effect.

Earlier two-year follow-up results from the trial were presented at the 2025 ESMO Congress in Berlin, Oct. 17-21, as abstract 1516MO. That analysis also reported durable disease control and T-cell responses with the combination.

The current evidence cannot show whether EVX-01 improves survival or how much of the response rate came from the vaccine rather than pembrolizumab. Those questions require larger controlled data.

Takeaway: Long-lasting responses are encouraging, but controlled evidence must show how much benefit comes from EVX-01 itself.