Personalized mRNA Melanoma Vaccine Cuts Recurrence Risk in Large Trial: Key Questions

A personalized mRNA vaccine given together with an immunotherapy drug lowered the risk of melanoma coming back or causing death by 42% over two years, according to results from a large clinical trial that Moderna and Merck announced Thursday. The Guardian reported that it is the first individualized cancer vaccine to show a positive result in a phase III trial, the large-scale testing stage that regulators require before approving a medicine.

The vaccine is not available outside research yet. Here are the main questions the results raise.

What did the trial find?

The trial, led from Australia, enrolled 1,137 patients, the Guardian reported. All had undergone surgery to remove their melanoma but were at high risk of the cancer returning. Every participant received an immunotherapy drug called pembrolizumab for twelve months, and some were also given the vaccine, known as intismeran. The Independent said the vaccine was tested alongside Merck's Keytruda.

Two years after treatment, 82% of patients who received the combination were alive and free of recurrence, compared with 70% of those who received the immunotherapy drug alone, according to the Guardian. The Independent put the first figure at 82.2%. It also reported that the combination lowered the risk of the cancer spreading by 38%.

How does a personalized vaccine work?

Each dose is made for one patient. According to the Independent, the vaccine is based on the unique mutations in that person's tumor and instructs the patient's cells to produce copies of them, so the immune system learns to find and destroy cells carrying those changes. Keytruda works differently: it removes a natural brake that cancer cells use to hide from immune attack.

Dr. Jessamy Tiffen of the Centenary Institute, who was not involved in the research, told the Guardian the vaccine targets up to 34 gene mutations specific to each patient. In the trial, nine doses were given, starting 13 weeks after surgery, the Independent reported.

What do experts say, and what are the limits?

Prof. Georgina Long of the Melanoma Institute Australia, who will present the data, called the findings “a foundational shift in our approach to cancer.” Dr. Hussein Tawbi of the University of Texas MD Anderson Cancer Center, a trial investigator, said the difference between the groups was highly significant statistically and not a matter of chance, the Independent reported.

Others urged caution. Tiffen noted that a significant share of patients do not respond to the vaccine at first and that cancer cells can adapt to treatment, so it is not yet known how well the approach performs beyond two years. Prof. Christopher Sweeney of Adelaide University said further research is needed to see whether it works in patients who have visible cancer or who do not respond to the immune-boosting drug. The companies said it is too early to know whether the combination improves long-term survival, according to the Guardian.

The results have been accepted for publication in the New England Journal of Medicine and still have to go through peer review, the Guardian reported.

How did Moderna's stock react?

Moderna shares closed more than 17% lower Thursday after the findings leaked on an oncology website, the Independent reported, even though the stock had nearly quadrupled since August, when the trial's success was first announced without full data. Merck shares fell about 1.8%. Analysts had been looking for a reduction in recurrence risk of 40% or more. William Blair analyst Myles Minter described the move as a sell-on-the-news reaction and noted Moderna shares were still up 525% this year.

Why does it matter for people with melanoma?

Immunotherapy drugs have already raised survival rates for people with advanced melanoma in recent years, the Guardian noted. The new data suggest that adding a vaccine tailored to a patient's own tumor can lower the chance of recurrence further than the immunotherapy drug alone, at least over the first two years.

For patients, though, the practical picture is still distant. The vaccine will not become a standard melanoma treatment until it has gone through more study and regulatory review, which the Guardian said may take several years. Not everyone would benefit, according to Tiffen.

What happens next?

Long is scheduled to present the results Saturday at the European Society for Medical Oncology congress in Madrid. Moderna CEO Stephane Bancel told the Independent that the companies are preparing to file for U.S. regulatory approval and expect to launch the vaccine in 2027.

Around Prague, based on reporting by The Independent, The Guardian