Experimental mRNA vaccine cuts risk that melanoma returns by 42%

Personalized mRNA Vaccine Shows Major Promise Against Melanoma Recurrence

Earthguardiansonline.com – A personalized mRNA treatment combined with the immunotherapy drug Keytruda reduced the risk of melanoma returning after surgery, or of death, by 42% in a late-stage clinical trial. The finding could mark an important step toward cancer treatments designed around the genetic features of an individual patient’s tumor.

The experimental vaccine, currently known as intismeran autogene, was developed by Merck and Moderna. Results from the melanoma study are scheduled for presentation Saturday in Madrid during a meeting of the European Society for Medical Oncology. The companies released the results Thursday and said they are in discussions with regulators, signaling that a submission to the US Food and Drug Administration could follow.

Unlike vaccines intended to prevent infections, this treatment is designed for people who have already had cancer removed surgically. Its purpose is to help the immune system recognize and attack any cancer cells that may remain in the body after surgery.

A vaccine built around each tumor

The technology relies on mRNA, the same broad platform used in Moderna’s Covid-19 vaccine. But instead of teaching the body to identify a virus, the melanoma vaccine is tailored to the unique genetic profile of a patient’s cancer.

After a tumor is removed, scientists sequence a sample and look for markers that are most likely to provoke an immune response. Those markers are then used to create a vaccine for that individual. The goal is a highly specific immune attack directed at the patient’s own cancer cells.

“This personalized cancer vaccine is a specific type of treatment that boosts the body’s immune response only against the cancer cells that are there,” Dr. Michael Postow said. “It is a much more targeted immune boost directly against that patient’s individual tumor.”

Postow, chief of the melanoma service at Memorial Sloan Kettering Cancer Center, worked with patients enrolled in the trial. He described the treatment as an approach unlike earlier cancer vaccines because of both its individualized design and the effectiveness seen so far.

“This new vaccine is something that we’ve never really seen before in terms of the efficacy that it has demonstrated and the way that it works,” Postow said.

How the study was conducted

The trial included 1,136 participants with melanoma that had been surgically removed. All participants received Keytruda, also known as pembrolizumab, an established immunotherapy medicine. Some additionally received the personalized mRNA vaccine, while others received a placebo.

The vaccine or placebo was administered by intramuscular injection every three weeks, for as many as nine doses. Keytruda was delivered through an intravenous infusion every six weeks for up to roughly one year. Because of the differing schedules, patients did not necessarily receive both treatments on the same day.

The reported 42% reduction in recurrence or death was measured after a median follow-up period of about two years. The trial is continuing so researchers can assess how durable the benefit remains over a longer period and better understand outcomes for participants over time.

Participants do not know whether they received the investigational vaccine or placebo. Beth Ryzyk, 59, was diagnosed with stage IIIC melanoma in December 2023 and took part in the study. More than a year after completing treatment, she remains cancer-free.

“I’m good; sometimes I even forget about it,” Ryzyk said. “It’s always in the back of your mind … but they’re watching.”

Ryzyk suspects she may have received the vaccine because she felt mildly unwell after treatments, with flu-like symptoms and fatigue the following day. However, because the study is blinded, she does not yet know which treatment she received.

Why preventing recurrence matters

For people with higher-risk melanoma, surgery may remove all visible disease but cannot guarantee that cancer will not return. Stage IIIC melanoma indicates that the cancer had certain features in the skin and had reached nearby lymph nodes, a combination that increases the chance of recurrence.

Melanoma can return in lymph nodes or spread to distant organs, including the lungs, liver, bones, or brain. This is why patients may receive treatment after surgery in what clinicians call the adjuvant setting: therapy intended to lower the risk of cancer coming back after the primary tumor has been removed.

“We wish that surgery alone would be curative, but we know from many, many studies that patients in that situation have a very high likelihood of it coming back at some place,” Postow said.

Keytruda transformed treatment options for several cancers after its approval in 2014. The drug works by blocking a pathway that can prevent immune cells from attacking cancer. It became widely known after being used in the treatment of former President Jimmy Carter, whose melanoma had spread to his liver and brain. Carter announced in December 2015 that he was cancer-free.

The new trial suggests that pairing Keytruda with a personalized vaccine could strengthen the immune response beyond what immunotherapy alone can achieve in some patients. Keytruda removes one barrier to immune activity, while the mRNA vaccine may help direct that activity toward the specific tumor markers found in each person’s cancer.

Potential implications beyond melanoma

The melanoma findings have drawn attention because they offer one of the clearest demonstrations to date that personalized mRNA cancer vaccination may provide a meaningful clinical benefit. The approach also represents a different model for oncology treatment: rather than giving every eligible patient exactly the same therapy, the vaccine is manufactured around the molecular characteristics of a single tumor.

Merck and Moderna are studying the technology in other cancers, including lung and pancreatic cancer. Those investigations are still ongoing, and results in melanoma do not establish that the same benefit will occur in every cancer type. Each disease has different biology, treatment challenges, and patterns of immune response.

For melanoma patients, the findings remain encouraging but do not yet mean the vaccine is broadly available. Regulatory review, longer-term trial follow-up, and further clinical evaluation will help determine whether intismeran autogene becomes a standard option after surgery.

If approved, the treatment could give patients facing a high risk of recurrence another way to pursue protection after surgery. Its progress also reinforces the wider potential of mRNA technology—not only as a tool against infectious disease, but as a way to create more individualized cancer therapies.