A vaccine based on messenger RNA (mRNA) technology reduces the possibility of melanoma recurrence by almost 50%. This new strategy significantly enhances the effects of standard treatment, according to the results of a study presented at the annual meeting of the American Society of Clinical Oncology (ASCO 2026) held in Chicago. The details of the work have also been published in the Journal of Clinical Oncology.
The new study reveals that the combination of this vaccine, called intismeran (Moderna) and the anti-PD-1 immunotherapy pembrolizumab (MSD) is effective in reducing the risk of recurrence and death from this type of skin cancer by 49% compared to treatment with pembrolizumab alone
Data from this phase IIb clinical trial called Keynote-942 were obtained after five years of follow-up.
Reduces recurrences and deaths
According to the study results, 68.8% of patients treated with the therapeutic combination remained cancer-free five years after surgery, compared to 49.1% of those who received only pembrolizumab. Consequently, the incorporation of intismeran into biological treatment reduced the risk of recurrence or death by 49%.
In addition, the combined therapy reduced the risk of developing distant metastasis by 59%. Regarding overall survival, defined as the absence of death from any cause, reached 92.2% in the group that received the vaccine along with immunotherapy, compared to 71.3% among patients treated only with immunotherapy.
For Janice Mehnert, lead researcher and professor at the Department of Medicine at the Grossman School of Medicine at New York University, the study "provides solid evidence" that this strategy "can reduce the risk of cancer recurrence and improve clinical outcomes".
She highlights that the results support research on this type of strategy, as they "demonstrate that mRNA vaccines like intismeran could work well in combination with immunotherapy for other types of cancer with high mutation rates that have been difficult to target".
Mechanism
The study results highlight the key role of T cells, a type of lymphocyte capable of recognizing and destroying both viruses and tumor cells. To prevent damage to healthy tissues, the immune system has regulatory mechanisms, known as immune checkpoints, that dampen the activity of these cells once the infection is cleared.
However, cancer cells can exploit these mechanisms to their advantage, activating these checkpoints to evade immune surveillance. In this context, immunotherapies based on checkpoint inhibitors, such as pembrolizumab, block the PD-1 receptor-mediated interaction, restoring the ability of T cells to recognize and attack tumor cells.
However, the efficacy of PD-1 inhibitors is limited in some patients, as tumor cells can develop immune escape mechanisms that allow them to resist the action of these treatments.
To overcome this limitation, researchers have explored complementary strategies, including therapeutic vaccines. Intismeran uses mRNA technology to train the immune system to identify and attack tumor cells.
The vaccine was designed to induce an immune response targeted against neoantigens, abnormal proteins generated by mutations present exclusively in cancer cells. In this way, the aim is to enhance tumor recognition by the immune system and strengthen the anti-tumor activity of T cells.
Personalized vaccine
Since all participants had previously undergone surgery to remove melanoma, researchers were able to analyze the molecular characteristics of each tumor and identify up to 34 specific neoantigens per patient. Based on this information, they developed a personalized mRNA vaccine tailored to the individual tumor profile of each participant.
The vaccine induced the generation of T lymphocytes targeted against the neoantigens encoded by the mRNA, thus enhancing the immune system's ability to recognize and eliminate residual melanoma cells that could lead to a recurrence or disease spread.
According to Mehnert, a phase III multicenter trial is currently underway to evaluate the efficacy of intismeran in combination with pembrolizumab as first-line treatment for melanoma. Additionally, this vaccine strategy is also being investigated in other solid tumors, including lung cancer, to determine its ability to prevent disease recurrence.
The Keynote-942 trial included patients recruited between 2019 and 2021 at oncology centers in Australia and the United States. All participants had undergone surgery. During follow-up, seven patients in each treatment group died, mainly as a result of cancer progression. In terms of safety, the adverse effects were considered manageable and consisted mainly of fatigue, reactions at the injection site, and chills.
"Important study"
To gather independent assessments, SMC Spain consulted Luis Álvarez Vallina, head of the Clinical Research Unit in Cancer Immunotherapy at the National Center for Oncological Research CNIO-Hospital del Mar, and Manel Juan, head of the Immunology Service at Hospital Clínic. Both agree on the relevance of the study.
According to Álvarez Vallina, this phase IIb trial is probably "one of the most important studies to date on personalized RNA vaccines based on neoantigens," he says. He also emphasizes that the study "provides mechanistic data that reinforce the biological basis" of this therapeutic strategy.
"The relevant aspect is that, unlike other adjuvant immunotherapy combinations, here we do see a sustained reduction in the risk of recurrence and metastasis. If the phase III clinical trial confirms these results, it could establish the first real standard for personalized RNA vaccines in oncology," says the CNIO researcher.