A world-first mRNA cancer vaccine has dramatically cut the risk of melanoma recurrence and death in a landmark large-scale trial that signals a new era in personalised cancer medicine.
The Australian-led Phase 3 trial found that adding a tailor-made cancer vaccine reduced the risk of the recurrence of melanoma or death by 42 per cent, compared with patients who were only given the immunotherapy drug, pembrolizumab (sold as Keytruda).
Principal investigator, Professor Georgina Long, said she almost fell off her chair when she got the phone call relaying the trial results.
“I’m not one prone to exaggeration, but this really is a very, very big leap forward in cancer,” said Long, who pioneered immunotherapy treatments that transformed melanoma from a death sentence to a treatable disease.
“It’s all the clichés: landmark moment, moon landing, first flight – it really is a foundational shift,” she said from her apartment in Lisbon, Portugal, on sabbatical from her medical director role at the Melanoma Institute Australia, affiliated with the University of Sydney.
Trial participants had all previously undergone surgery to remove their melanoma tumours. All 1137 were given pembrolizumab. Two thirds were also given the personalised mRNA therapeutic vaccine designed to enable their immune system to recognise and destroy their distinct cancer cells, while the remaining patients were given a placebo injection.
The trial, funded by Merck and Moderna, found that at two years, 82 per cent of trial patients who received both treatments were alive and melanoma-free, compared with 70 per cent of those who received pembrolizumab alone.
Australian mRNA Cancer Vaccine Hub Director Associate Professor Seth Cheetham said the combination of immunotherapy and the personalised cancer vaccine was an “incredible breakthrough” that would help usher in a new era in cancer research and treatment.
“This is the first really large trial that’s shown definitively that this technology works, it reduces the risk of recurrence or spread and results in better outcomes compared to standard of care,” Cheetham said.
“This is really the gold standard, and it’s what the entire field’s been waiting on,” he said.
Before checkpoint immunotherapies such as pembrolizumab – pioneered by Long’s research in the field – advanced melanoma was largely a death sentence, with most patients surviving less than a year. Today, around half of patients with advanced melanoma are alive and effectively cured, but around half still die from the disease.
Long has dedicated her career to the mission of zero deaths from melanoma, and to finding a cure for these treatment-resistant patients. She won Australian of the Year in 2024 with her colleague and friend, the late Professor Richard Scolyer.
The new therapeutic vaccine is not for people who have never had cancer – it’s designed to help protect patients against their melanoma recurring once their tumour has been removed.
Pembrolizumab helps the body hunt down cancerous cells, which can evade the immune system by mimicking healthy cells. The vaccine goes a step further, by telling immune cells exactly what the cancer cells look like.
The personalisation of the vaccine is critical, Long said.
Trial researchers sequenced the genome of each person’s tumour and compared it with their healthy cells to pinpoint the unique combination of mutations on the surface of their cancer cells, called neoantigens.
They used this information to create tailor-made vaccines that would teach the immune system how to recognise those neoantigens as a threat to be destroyed.
Cheetham said: “It really is the antithesis of a one-size-fits-all approach, which has dominated cancer care for a long time.”
“It’s pioneering a new kind of medicine, in which we are looking at each tumour individually and crafting a unique treatment for it,” he said.
Manufacturing such a personalised drug will be a logistical challenge, Cheetham said, especially for sick patients who will need timely access.
The trial’s interim analysis was presented at the European Society for Medical Oncology on Sunday, ahead of publication in the New England Journal of Medicine.
In August, news of the trial’s success saw Moderna’s shares surge more than 170 per cent in a single trading day. But on Friday, after the trial’s results were leaked by an oncology website ahead of embargo, the company’s shares plunged by more than 25 per cent, in a phenomenon stockbrokers call “buy the rumour, sell the fact”.
The vaccine was generally well tolerated in patients. Long said she hoped the findings could also help patients with active advanced melanoma or other cancers, but research is ongoing.
Cheetham said melanoma cells were among the most promising targets, due to their abundance of mutations that make them appear quite distinct from healthy cells, whereas other cancers may not be as susceptible.
But early trials of mRNA vaccines to treat lung and pancreatic cancers have some researchers optimistic, Cheetham said.
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