A personalized mRNA cancer vaccine combined with immunotherapy reduced the risk of melanoma recurrence or death by 49% at five years, according to updated results from a Phase 2b clinical trial.
The findings, from the KEYNOTE-942 trial, showed that 68.8% of patients who received the vaccine intismeran autogene (mRNA-4157) plus pembrolizumab (Keytruda) remained cancer-free after five years, compared with 49.1% of those who received pembrolizumab alone.
The combination also reduced the risk of distant metastasis by 59%. Overall survival was 92.2% in the combination group versus 71.3% in the immunotherapy-only group, per the NYU Langone Health press release.
The trial tested the personalized vaccine in patients with high-risk resected Stage III/IV melanoma.
NYU-Led Trial: Personalized mRNA Vaccine
Researchers at NYU Langone Health and its Perlmutter Cancer Center led the effort, in collaboration with sites in Australia and the United States. The vaccine is tailored to each patient’s tumor by identifying up to 34 unique neoantigens and using mRNA technology to train the immune system to target cancer cells.
“Our study offers strong evidence to melanoma patients that intismeran vaccine therapy, when used in combination with immunotherapy, can demonstrably reduce their risk of having their cancer return and improve clinical outcomes,” said study senior investigator Janice Mehnert, MD, professor in the Department of Medicine at NYU Grossman School of Medicine and director of the melanoma medical oncology program at Perlmutter Cancer Center.
The results were presented at the American Society of Clinical Oncology annual meeting and published in the Journal of Clinical Oncology.
Melanoma Strikes Hard: Cases and Projections for 2026
At least one in five Americans will develop some form of skin cancer by the age of 70, per the Skin Cancer Foundation.
In the United States, melanoma remains a significant health concern. The American Cancer Society projects that about 112,000 new melanomas will be diagnosed in 2026 (65,400 in men and 46,600 in women), with approximately 8,510 deaths (5,500 men and 3,010 women).
Melanoma accounts for only about 1% of skin cancers but causes the large majority of skin cancer deaths. Death rates have declined rapidly in recent years due to advances in treatment, including immunotherapy.
The risk of developing melanoma increases with age, with the average age at diagnosis around 66. However, it is one of the most common cancers in young adults, particularly young women.
From ages 15 to 39, men are 55% more likely to die of melanoma than women in the same age group. After age 50, incidence is higher in men.
Globally, melanoma incidence and mortality are highest in regions with fair-skinned populations and high UV exposure. Australia and New Zealand report the highest incidence rates, per the World Cancer Research Journal. New Zealand has recorded some of the highest mortality rates for melanoma.
Prevention and Promise: Sun Protection Still Key
Prevention focuses on reducing ultraviolet (UV) exposure. Key measures include seeking shade, wearing protective clothing, and using broad-spectrum sunscreen with SPF 30 or higher.
Avoiding tanning beds is critical; people who use a tanning bed before age 35 increase their melanoma risk by 75%, according to the Melanoma Research Alliance. Regular skin self-exams and professional checks are also recommended for those at higher risk.
The vaccine approach builds on mRNA technology. It is one of several personalized cancer vaccines under study. A Phase 3 trial is underway to evaluate intismeran as a first-line therapy in combination with pembrolizumab. Researchers are also exploring its use in other cancers.
Side effects in the KEYNOTE-942 trial were considered manageable and included fatigue, injection-site pain, and chills.
These five-year results provide the longest follow-up data yet for this personalized mRNA vaccine strategy in melanoma.
