Among therapeutic approaches for melanoma vaccines presented at ESMO Congress 2025 were one off-the-shelf and one personalized.
Jessica Hassel, MD, presented primary results of IOB-013/KN-D18 (NCT051552254), a phase 3 study of IO102-IO013, an off-the-shelf, immune-modulatory cancer vaccine plus pembrolizumab for first-line treatment of advanced melanoma (LBA53). IO102-IO1-3 targets both indolamine-2,3-dioxygenase (ID01) and programmed cell death ligand 1 (PD-L1)-positive tumor cells and immune-suppressive cells within the tumor microenvironment. Individuals with untreated, advanced melanoma were randomly assigned to vaccine plus pembrolizumab (n=203) or pembrolizumab (n=204) for up to 2 years.
Progression-free survival (PFS), the primary endpoint, after a median follow-up of 23 months was 19.4 months in the vaccine arm vs 11.0 months in the pembrolizumab arm (HR 0.77; 95% CI 0.58-1.00; P=.0558). Improvement in PFS favored the combination across subgroups including those with negative PD-L1 (median PFS 16.6 months vs 3.0 months), mutated BRAF V600, elevated LDH, or anti-PD-1 treatment naïve.
Overall response rate (ORR) was 91% for the combination and 84% for pembrolizumab. Adverse events (AE) associated with pembrolizumab were as expected; IO102-IO013 did not add to these, other than injection site reactions. Vaccine-specific immune responses were expanded in the vaccine arm and not in the pembrolizumab arm.
Dr. Hassel concluded that the data support a potential benefit of an immune-modulatory cancer vaccine in combination with pembrolizumab in patients with untreated advanced melanoma.
Discussant Ines Pires da Silva, MD, PhD, pointed out that although this new concept, an immune-modulatory vaccine, did not significantly increase PFS overall, 4 subgroups did benefit, which could be clinically significant. She would like to see predictive baseline markers, the best population to treat, and better immunomodulatory targets identified.
Muhammad Khattak, MBBS, presented 2-year follow-up data from a phase 2 trial of EVX-01, a personalized peptide-based neoantigen vaccine in combination with pembrolizumab in stage III/IV, unresectable melanoma (n=16; Abstract 1516MO).
Seven to 10 optimal patient-specific neoantigens were identified using Evaxion’s AI-Immunology™. Patients received pembrolizumab while their EVX-01 was manufactured and during 6 priming doses followed by 4 boosting doses of vaccine. There were no grade ≥3 AE attributed to EVX-01; and 1 grade 3 for pembrolizumab.
The best ORR was 75%, with 100% manufacturing success. Response was 92% at 24 months of follow-up; 3 discontinued with progressive disease, 1 from intra-cranial hemorrhage. Conversion rate (deepened response) was 54%; 81% of the predicted neoantigens induced T cell responses. Dr. Khattak concluded the results support continued development of EVX-01 in high-risk melanoma.
Discussant Dr. Dirk Jager, said the rate of T cell responses was really impressive, suggesting the prime-boost concept is effective. He questioned whether there was an objective criterion to observe the 54% conversion rate on checkpoint blockade. Randomized data are needed to define a deepening effect. There should be differentiation between CD4 and CD8 responses. Biopsies would clarify what is going on at the tumor sites during treatment.
If melanoma and other solid tumor vaccines fail in combination with checkpoint inhibitors, it will be necessary to define those subgroups most likely to experience response.
Dr. Lederman has no conflicts of interest to report.
Animation by Diana Connolly
