Melanoma, personalized mRNA vaccine: fewer recurrences in phase 3 study

A phase 3 study of a personalized mRNA therapeutic vaccine for melanoma has shown a 42% reduction in the risk of recurrence at two years, when the vaccine is added to immunotherapy with pembrolizumab compared with immunotherapy alone. The study, named INTerpath-001, involved 1,137 patients with high-risk melanoma enrolled at 157 centers worldwide, with Italy ranking first for the number of patients included.

According to the data presented, the vaccine-immunotherapy combination also reduced the risk of distant metastases by 38% compared with treatment with immunotherapy alone. This is an adjuvant therapy, meaning it is administered after surgical removal of the tumor, to reduce the likelihood of the disease recurring.

The vaccine is not a melanoma prevention tool: it is a personalized therapy built on the specific mutations of each patient’s tumor, designed to boost the immune response already activated by immunotherapy. Michele Del Vecchio, head of Medical Oncology for Melanomas at the Istituto Nazionale Tumori in Milan, described the research as “the first and only phase 3 study that has demonstrated that” an approach of this kind surpasses the results of standard therapy.

On the methodological level, some elements should be noted that define the current scope of the data. This is a phase 3 study, therefore in the advanced stage of clinical trials, conducted on a large, multicenter population, an element that strengthens the statistical reliability of the results compared with smaller or preliminary studies. The results were presented at the congress of the European Society for Medical Oncology, and full publication in the journal New England Journal of Medicine is expected in November: until that publication, the scientific community does not have access to the complete text of the study, the full methodological details, and any subgroup analyses, elements that allow for a more thorough independent evaluation of the data presented in summary form at the congress.

The material currently available does not report the maximum follow-up duration beyond the two years indicated, nor does it provide details on any adverse effects observed in the group treated with the vaccine compared with the control group, information that typically accompanies the full publication of a registrational study. Nor are there, in the material released so far, indications on the expected timeline for any application for authorization to regulatory bodies.

High-risk melanoma is one of the forms of skin cancer with the greatest likelihood of recurrence after initial surgery, which is why in recent years research has focused on adjuvant therapies capable of reducing this risk. The combined approach tested in INTerpath-001 is part of a line of research on therapeutic mRNA vaccines applied to oncology, a technology made available on a large scale during the Covid-19 pandemic and now the subject of trials in various types of cancer.

Publication in NEJM, expected in November, will allow for a more complete evaluation of the data, including a detailed analysis of the safety of the combined treatment.