Personalized Vaccine Under Study Shows Promise Against Melanoma

A clinical trial has revealed that combining a personalized mRNA vaccine with standard immunotherapy significantly cuts the risk of skin cancer recurrence or death in high-risk melanoma patients. The landmark five-year data from the “KEYNOTE-942 trial” shows that the combination therapy reduces the long-term risk of recurrence or death by nearly half, compared to standard treatment alone.

The results have captured the attention of clinicians worldwide, providing strong evidence that tailoring treatments to a patient's specific genetic tumor profile could represent the next frontier in oncological care. Experts note that these findings offer significant hope for managing aggressive forms of skin cancer.

"Melanoma is a skin cancer that can be very aggressive and deadly — and now there is therapy to treat it," explains Ingrid Herskovitz, M.D., dermatologist with Baptist Health Herbert Wertheim Cancer Institute, in a recent Baptist Health YouTube short. "And with these (study) results, scientists have shown that this therapy can reduce — by 50 percent —the possibility of the disease coming back or the person dying from melanoma."

The KEYNOTE-942 Trial: Long-Term Efficacy Unveiled

The study evaluated a combination regimen of an investigational mRNA-based personalized vaccine called “intismeran,” alongside the standard immunotherapy drug “pembrolizumab” (commercially known as Keytruda). Researchers tracked 157 patients who had previously undergone surgery to remove high-risk melanoma tumors.

Among the participants, 107 were randomly assigned to receive the combination of intismeran and pembrolizumab. The remaining 50 patients received only pembrolizumab, which reflects the current standard postoperative care for stage 3 or stage 4 melanoma patients.

The final five-year, follow-up data presented at the 2026 annual meeting of the American Society of Clinical Oncology (ASCO) in Chicago, and simultaneously published in the Journal of Clinical Oncology, confirmed a sustained, powerful treatment benefit:

• Cancer-Free Survival: 68.8 percent of patients receiving the vaccine-immunotherapy combination remained entirely cancer-free at five years, compared to just 49.1 percent in the immunotherapy-alone group.
• Risk Reduction: The addition of the personalized vaccine translated to a 49 percent reduction in the risk of cancer recurrence or death over the five-year tracking window.
• Metastasis Prevention: The combination therapy significantly hindered the disease from spreading, reducing the risk of distant metastasis—the migration of cancer cells to other vital organs—by 59 percent.
• Overall Survival: The overall survival rate reached 92.2 percent for the combination group, compared to 71.3 percent for those who received only standard immunotherapy.

"This study is very interesting because patients received surgery and ‘peismab’ [pembrolizumab], which is the center of care for these type of patients with stage-three melanoma — and some of them also received the vaccine," notes Dr. Herskovitz.

The Science of Custom-Built Cancer Vaccines

Unlike traditional vaccines designed to prevent infectious diseases, therapeutic cancer vaccines are engineered to treat an existing disease by training the patient's own immune system to recognize and destroy hidden cancer cells.

The vaccine used in this trial, intismeran, utilizes messenger RNA (mRNA) technology—the same chemical cousin to DNA used in modern viral vaccines—to deliver specific instructions directly to human cells.

What sets intismeran apart from standard oncological treatments is its highly tailored manufacturing process. Because every person's cancer has a distinct genetic makeup, the vaccine is custom-built for each individual recipient.

"The new thing about these vaccines is that they represent a personalized vaccine," says Dr. Herskovitz. "So, after the patient gets the surgery, the tumor gets processed in the lab for the proteins that are abnormal."

When a patient undergoes surgery to remove a melanoma tumor, researchers analyze the extracted cancer tissue to identify up to 34 distinct "neoantigens." Neoantigens are abnormal proteins produced strictly by cancer cells due to genetic mutations; they do not appear on healthy, normal body cells. By identifying these specific mutation markers, scientists can design an mRNA sequence tailored exclusively to that single patient's tumor footprint.

How Immunotherapy and mRNA Work in Tandem

To understand why the combination of a vaccine and an immunotherapy drug works so well, it is helpful to look at how cancer interacts with the human immune system.

The body naturally uses immune cells called T cells to patrol the bloodstream, hunt down viruses, and eliminate abnormal cells. To protect healthy tissues from accidental damage during an active immune response, the body utilizes specific "checkpoint" molecules on the surface of T cells that serve as biological off-switches.

While melanoma cells are highly abnormal, they are notoriously adept at hijacking these checkpoint molecules—specifically a protein receptor called PD-1. By binding to PD-1, melanoma cells effectively turn off the T cells, making themselves invisible to the body’s defenses and allowing the tumor to grow and spread unchecked.

Standard checkpoint inhibitors like pembrolizumab work by blocking the PD-1 receptor. This unmasks the cancer cells, making them visible to the immune system once again. However, melanoma can develop resistance to immunotherapy alone because the T cells still need to know exactly which targets to attack.

This is where the personalized mRNA vaccine comes into play. By introducing the mRNA instructions for the tumor's specific neoantigens, the vaccine forces the body to produce an army of T cells calibrated to seek out those precise abnormal proteins.

Dr. Herskovitz describes the bodily mechanism: "So, with this therapy it's like a little army going around the bloodstream looking for cells that are not normal, and they can be detected and eliminated from the patient's body."

Clinical Safety and the Path Forward

The data from the KEYNOTE-942 trial indicated that the side effects associated with adding intismeran to standard treatment profiles were highly manageable for patients. The most frequently documented adverse events included temporary fatigue, mild chills, and localized pain at the vaccine injection site—symptoms common to standard mRNA therapies. Seven patients in each tracking group passed away during the long-term follow-up period, primarily due to advanced cancer progression.

Led by senior investigators at NYU Langone Health and its Perlmutter Cancer Center, the success of this trial has opened up broader horizon for cancer research. A larger, multicenter phase 3 clinical trial is currently underway to evaluate whether the intismeran and pembrolizumab combination can safely serve as a primary, first-line therapy for newly diagnosed melanoma patients.

Moreover, because high mutation rates make certain malignancies difficult to treat, scientists are actively launching clinical trials to determine if personalized mRNA vaccines can prevent the recurrence of other aggressive conditions, such as non-small cell lung cancer and pancreatic cancer.

"The goal now is to have these technologies further explored in larger trials," says Dr. Herskovitz. "This is a very exciting time to be involved in care of these patients with these promising technologies."