The risk of melanoma returning is higher for what doctors call “high-risk” melanoma. This usually means stage IIB or IIC (a thick tumor in the skin that hasn’t spread), stage III (melanoma that reached nearby lymph nodes, the small bean-shaped glands that are part of your immune system), or stage IV (melanoma that spread to distant parts of the body). The new study included people at all of these stages, as long as surgeons had removed all the cancer they could find.

WATCH: Melanoma Treatment Has “Come a Long Way”

Everyone in the study had cutaneous melanoma, meaning it started in the skin. The results don’t apply to melanoma that starts in the eye or inside the body, such as in the mouth or nose.

What Treatment After Surgery Looks Like Today

Treatment given after surgery to lower the chance of the cancer returning is called adjuvant therapy. For high-risk melanoma, it’s usually immunotherapy, which means drugs that help your own immune system fight cancer.

The main options are drugs called checkpoint inhibitors such as pembrolizumab (Keytruda) and nivolumab (Opdivo). Cancer cells can switch on “brakes,” called checkpoints, that stop your immune cells from attacking. These drugs release those brakes so your immune system can go after the cancer, and treatment typically lasts about a year.

If your melanoma has a BRAF mutation (a change in a gene that helps the cancer grow) and is stage III, targeted pills called dabrafenib (Tafinlar) and trametinib (Mekinist) may be another option, so ask whether your tumor was tested.

These treatments help many people. But some still see their melanoma come back. That’s why researchers have been looking for ways to make immunotherapy work even better. Earlier large trials that added a second checkpoint inhibitor didn’t improve results, so researchers turned to a different approach.

What Is a Neoantigen and Why Does It Matter?

As cancer grows, its DNA picks up mistakes, called mutations. Some of these mistakes lead cancer cells to make unusual proteins that your healthy cells don’t have. Small pieces of these proteins are called neoantigens (“new antigens”). An antigen is anything your immune system can learn to recognize as a target.

Neoantigens matter because they work like name tags that only your cancer cells wear. If your immune system learns to spot them, it can go after the cancer while leaving healthy cells alone.

The catch is that every person’s cancer has its own set of mutations. A vaccine that targets neoantigens must be made individually for each person.

WATCH: The Genetic Mutation That Drives Melanoma

How Your Personalized Vaccine Is Made

Moderna and Merck are developing intismeran autogene, or intismeran. Dr. Long describes it simply: “That fingerprint is read by sequencing the tumor, then a ‘wanted poster’ of the cancer is made as mRNA, showing the immune system exactly what to look for and attack.”

According to a recent paper describing the process, written by scientists at those companies, here’s how it works:

1. A small piece of the tumor removed during your surgery is sent to a lab, along with a small blood sample (less than a teaspoon).
2. The lab reads the DNA of both. Your blood serves as a “normal” comparison, so the lab can pick out changes found only in the cancer.
3. A computer program selects up to 34 neoantigens most likely to trigger a strong immune response.
4. The instructions for all of them are written into a single mRNA strand, wrapped in tiny fat bubbles called lipid nanoparticles, and shipped to your treatment center.
5. You get the vaccine as a shot in the upper arm or thigh muscle.

People don’t have to wait for the vaccine to be made before starting treatment. In the new study, patients began Keytruda right away and added the vaccine once it was ready. Half received their first vaccine dose within about two months (64 days), and the other half waited longer. The lab was able to make a vaccine for more than 99% of patients.

How This Differs From a Flu Shot

Most vaccines you know, like flu or measles shots, are preventive. They’re given to healthy people so they don’t get sick.

Intismeran is a treatment vaccine. It’s given to people who’ve already had cancer, to train the immune system to hunt down any cancer cells that may remain.

As Dr. James Larkin, scientific co-chair of the ESMO Congress 2026, who was not involved in the study, put it: “This is very different from vaccinating individuals without cancer to reduce the risk of subsequent cancer development.”

It’s also an mRNA vaccine. mRNA, or messenger RNA, is a set of instructions that tells your cells to make a specific protein. Here, the proteins are your tumor’s neoantigens, which teach your immune system what to look for. Your body breaks down the mRNA after it does its job, and it doesn’t change your DNA. Some COVID-19 vaccines use the same basic technology.

What the Study Found

This study grew out of an earlier, smaller trial called KEYNOTE-942. In that phase 2b study (a mid-stage trial that tests whether a treatment seems to work), adding the vaccine to Keytruda cut the risk of melanoma coming back by 49% after three years of follow-up.

INTerpath-001 was a phase 3 study. That’s the large, final stage of testing that’s usually needed before a treatment can be approved. It included 1,137 adults with high-risk melanoma that had been removed with surgery. About two out of three (757 people) got Keytruda plus the vaccine. The rest (380 people) got Keytruda plus a placebo, a look-alike shot with no medicine in it. Neither patients nor their doctors knew who got which.

The main goal was recurrence-free survival. That’s how long people live without the cancer coming back. It’s one of the most important measures after surgery, because the whole point of treatment at this stage is to keep the cancer away.

Researchers presented the results on October 24 at the European Society for Medical Oncology (ESMO) Congress 2026, a major cancer meeting. After about two years:

• About 82 out of 100 people who got the vaccine plus Keytruda were alive with no sign of melanoma, compared with about 70 out of 100 who got Keytruda alone.
• Overall, the risk of the cancer coming back (or of dying) was 42% lower with the combination.
• The vaccine also lowered the risk of melanoma spreading to distant parts of the body (or of dying) by 38%. About 89 out of 100 people in the vaccine group were free of distant spread, compared with about 80 out of 100 in the Keytruda-only group.
• The benefit looked similar whether people had earlier-stage or later-stage high-risk melanoma.

However, the benefit didn’t show up right away. In the first six months, the cancer came back at about the same rate in both groups. The difference appeared after that. Researchers think this is because of the wait for the vaccine, and because the immune system needs time to respond.

“The data from INTerpath-001 represent a major advance for the adjuvant treatment of stage II and III melanoma; the reduction in risk of relapse is clinically significant,” said Dr. Larkin.

It’s too early to know whether the vaccine helps people live longer. So far, survival differs statistically significantly between the two groups, and two years is also a fairly short time. Researchers will continue to follow these patients.

“For a patient, more time free of melanoma is a meaningful benefit in its own right,” Dr. Long said. “Longer follow-up is needed to show an impact on melanoma-specific and overall survival, as well as whether the early benefit we are seeing across stages and subgroups holds, and which patients benefit most.”

Side Effects

Severe side effects, which doctors call grade 3 or higher, happened in about 24% of people on the combination and about 20% on Keytruda alone. These side effects are strong enough to require medical care or limit daily activities.
The most common side effects with the vaccine were:

Fever, in about half of people, compared with about 8% on Keytruda alone

• Pain where the shot was given, in about half, compared with about 1 in 10 in the Keytruda-only group, who received a placebo shot
• Tiredness, in about 39%, compared with about 30%

According to the researchers, side effects from the vaccine shots were generally mild and short-lived.

Can You Get It Now?

Not yet. Intismeran is still investigational, which means it hasn’t been approved by the U.S. Food and Drug Administration (FDA). The companies have said they plan to talk with regulators about seeking approval.

For now, the only way to get it is through a clinical trial. INTerpath-001 is no longer enrolling, but other studies of this vaccine are underway. Your doctor can help you find out if any are open to you.

Clinical trials are already ongoing in lung, bladder, and kidney cancer testing the effectiveness of intismeran in combination with pembrolizumab.

Questions To Ask Your Doctor

You can’t ask for this vaccine at your next appointment just yet. But these questions can help you understand where you stand now, and be ready if it’s approved:

• Am I a candidate for a personalized vaccine like this, either in a trial now or if it’s approved later?
• Was my tumor tissue from surgery saved, and could it be used to make a vaccine?
• How long would it take to make my vaccine, and would I start immunotherapy while I wait?
• Is there a clinical trial I could join right now?
• Was my tumor tested for a BRAF mutation, and how does that change my options?

This research is still unfolding. But for people facing the worry of melanoma coming back, it’s real progress, and it’s worth keeping on your radar.

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