A groundbreaking combination of a personalized cancer vaccine and immunotherapy has demonstrated the ability to cut melanoma recurrence risk by nearly half, with benefits sustained over five years. The findings represent a significant advance in preventing one of the deadliest skin cancers from returning after surgical removal.

How Does This New Melanoma Treatment Work?

The approach combines two immune-boosting strategies. The vaccine, called intismeran, is custom-made for each patient based on their individual tumor's genetic makeup. Researchers analyze tumors for up to 34 unique abnormal proteins, called neoantigens, that are specific to each person's cancer. The vaccine then teaches the immune system to recognize and attack these cancer-specific proteins. When paired with pembrolizumab (Keytruda), an immunotherapy drug that removes the "brakes" cancer cells use to hide from the immune system, the combination creates a powerful one-two punch.

The study, called KEYNOTE-942, enrolled 107 melanoma patients who received the combination therapy after surgery, compared with 50 patients who received pembrolizumab alone. After five years of follow-up, the results were striking:

• Cancer-Free Survival: 68.8% of patients receiving the combination therapy remained cancer-free, compared to 49.1% in the pembrolizumab-only group
• Recurrence Risk Reduction: Adding the vaccine reduced the risk of cancer returning or causing death by 49%
• Spread Prevention: The combination reduced the risk of cancer spreading to distant parts of the body by 59%
• Overall Survival: 92.2% of the combination group survived without cancer-related death, versus 71.3% in the immunotherapy-alone group

The research was presented at the 2026 annual meeting of the American Society of Clinical Oncology on June 1 and published simultaneously in the society's Journal of Clinical Oncology.

Why Does Personalized Immunotherapy Matter for Melanoma?

Melanoma is notoriously difficult to treat because cancer cells are skilled at evading the immune system. Standard immunotherapies like pembrolizumab work well for some patients but not others, as melanoma cells can develop resistance over time. By creating a vaccine tailored to each patient's unique tumor mutations, researchers can train the immune system to recognize cancer cells that might otherwise escape detection.

"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 Dr. Janice Mehnert, a professor in the Department of Medicine at NYU Grossman School of Medicine.

Dr. Janice Mehnert, Professor of Medicine at NYU Grossman School of Medicine

The study also highlighted how the vaccine works at the cellular level. T cells, which are immune cells capable of attacking both viruses and cancers, are central to the strategy. Cancer cells typically hijack checkpoint molecules on T cell surfaces to "turn off" immune attacks. Pembrolizumab blocks these checkpoints, making cancer cells visible to the immune system again. The vaccine then provides specific targets for T cells to attack.

What Are the Side Effects and Next Steps?

Side effects from the combination therapy were manageable and included fatigue, pain at injection sites, and chills. Seven patients in each treatment group died during the five-year follow-up, with most deaths attributed to cancer.

The promising results have already sparked larger studies. A phase 3 trial is underway to test whether intismeran works as a first-line treatment for newly diagnosed melanoma patients. Researchers are also exploring whether the vaccine approach can prevent recurrence in other cancers with high mutation rates, including lung cancer.

"Our findings also serve as encouragement to cancer researchers globally that mRNA vaccines like intismeran could work well in combination with immunotherapy for other cancers whose high rates of mutations have proven difficult to target," Dr. Mehnert added.

Dr. Janice Mehnert, Professor of Medicine at NYU Grossman School of Medicine

What's the Broader Context for Skin Cancer?

Melanoma remains the most serious form of skin cancer, though the outlook has improved dramatically in recent years. The United States is expected to see approximately 112,000 new melanoma cases in 2026, with about 65,400 occurring in men and 46,600 in women. Melanoma deaths have declined sharply over the past decade, largely due to advances in immunotherapy and targeted treatments like this new vaccine approach.

The KEYNOTE-942 trial enrolled patients from cancer centers in Australia and the United States between 2019 and 2021, all of whom had undergone surgery to remove their melanoma tumors. The five-year follow-up data provides strong evidence that the benefits of combination therapy persist long-term, offering melanoma patients a meaningful new option for reducing their risk of recurrence after surgery.