‘Bespoke’ mRNA vaccine significantly reduces risk of melanoma recurrence or death, clinical trial shows

Trial results represent ‘foundational shift’ in approach to cancer, allowing scientists to harness immune system in more personalised way

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A personalised mRNA-based melanoma vaccine significantly reduces the risk of cancer recurrence or death within two years, new clinical trial results show.

The vaccine, intismeran, is custom-made to target genetic mutations unique to an individual’s melanoma. It is the first individualised cancer vaccine to show positive results in a phase III clinical trial.

The Australian-led trial included 1,137 patients whose melanoma had been surgically removed but were at high risk of it returning.

All were treated with an immunotherapy drug called pembrolizumab for twelve months, and some were also given the personalised intismeran vaccine.

The trial found that at two years post treatment, the combination of intismeran and pembrolizumab reduced the risk of melanoma recurrence or death by 42% compared with treatment with pembrolizumab alone.

Prof Georgina Long, medical director at the Melanoma Institute Australia and 2024 Australian of the Year, described the findings as “a foundational shift in our approach to cancer”, allowing scientists to “harness … the immune system in a more personalised way to reduce the risk of melanoma recurrence or death. This has not been achieved before in the history of cancer drug development.”

Long will present the results at the European Society for Medical Oncology’s annual congress in Madrid on the weekend.

The results have been accepted for publication in the New England Journal of Medicine and will need to go through a process of peer review.

Patients in the trial – conducted across 157 sites worldwide – had not previously received any cancer drug treatment. Of those receiving the combination of intismeran and pembrolizumab, 82% were alive and recurrence-free after two years, compared with 70% of participants treated with pembrolizumab alone.

In a phase III trial, a treatment is tested in a large group of people and compared with standard treatments; it is necessary before drug regulators can approve a medicine for use in the general population.

In recent years, developments in immunotherapy drugs have significantly increased survival rates for people with advanced melanoma.

Dr Jessamy Tiffen, acting deputy director of the Centre for Cancer Innovations at the Centenary Institute, who was not involved in the research, said what was “truly remarkable” about the vaccine was the “deeply personalised nature of the treatment, something cancer researchers have been striving to achieve for decades”.

“Where previously oncologists could pick a targeted therapy based on a single gene mutation present in the melanoma, this bespoke mRNA vaccine targets up to 34 gene mutations, unique to each patient. This vaccine, in combination with another type of immunotherapy, then trains the immune system to recognise and eliminate the melanoma, and most importantly, stop it from coming back.”

She noted that the treatment, if progressed, would not benefit all people with melanoma. “A significant portion do not respond to the vaccine in the first instance,” she said.

“Cancer cells also have an insidious ability to adapt and evade whatever treatment we throw at them. Only time will tell how effective the treatment is beyond two years, but the results are clear that the combination works better than immunotherapy alone, and that’s a very exciting development.”

The drug manufacturers said it was too early to tell from the data whether the combination treatment improved long-term survival.

Prof Christopher Sweeney, director of the South Australian immunoGENomics Cancer Institute at Adelaide University, described the vaccine as “a step-change approach for how to improve the body’s immune system to see cancer cells as foreign and then augment the ability to prevent the cancer cells growing and recurring”.

He said more research was needed to see if the approach was effective in patients “who have cancer we can see”, or who were not responsive to the immune enhancer pembrolizumab.

The personalised vaccine will not be available as a standard melanoma treatment until it has gone through further study and regulatory review, a process that may take several years.