An mRNA-based vaccine that is personalised to target each patient’s specific cancer has been shown to reduce the risk of recurrence or death by 42% two years after starting treatment, according to results from a phase III clinical trial which will be presented at the European Society for Medical Oncology Congress this weekend.

An mRNA-based vaccine that is personalised to target each patient’s specific cancer has been shown to reduce the risk of recurrence or death by 42% two years after starting treatment, according to results from a phase III clinical trial which will be presented at the European Society for Medical Oncology Congress this weekend.

The international trial included 1137 patients whose melanoma had been surgically removed, but who were at very high risk of it returning (stage IIB to IV). It compared outcomes for patients who were given the therapeutic cancer vaccine intismeran alongside pembrolizumab immunotherapy versus treatment with pembrolizumab alone.

Intismeran is designed specifically for each patient, based on the unique identity of their tumour, to train and activate the immune system to recognise and fight cancer.

How it works

Lead investigator Professor Georgina Long AO, Medical Director at Melanoma Institute Australia (MIA) and Chair of Melanoma Medical Oncology and Translational Research at The University of Sydney, said abnormal proteins, called neoantigens, give every melanoma its own unique identity, like a fingerprint. The vaccine (also known as individualised neoantigen therapy) is created using mRNA technology.

“We analyse a sample of each patient’s tumour to read its unique neoantigen fingerprint, then create a ‘wanted poster’ of the cancer. This is delivered as mRNA, so the body’s own cells display the poster to the immune system, showing it exactly what to look out for and attack,” Professor Long said.

The findings

Overall, the trial showed that adding intismeran to pembrolizumab reduced the risk of melanoma recurrence or death by 42% compared with pembrolizumab alone.

For patients who remained recurrence-free beyond six months from the start of treatment, the reduction in the risk of recurrence or death was even greater, at 58% compared with pembrolizumab alone.

Pembrolizumab side effects were not increased by the vaccine and treatment was generally well tolerated, with the vaccine causing transient low grade side effects including injection site pain, headache, and chills in some patients.

Putting it in perspective

Experts say this new cancer vaccine technology represents a landmark shift with potential to change our approach not just to melanoma, but cancer more broadly.

“This trial is the largest-ever study to test this new cancer vaccine technology, and it shows significant efficacy. It therefore represents a landmark shift in the fight against cancer,” said Associate Professor Lisa Ebert is from the Centre for Cancer Biology at Adelaide University.

Experts said the vaccine is particularly unique as it is custom-manufactured and individually designed.

“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,” said Dr Jessamy Tiffen, Head of the Centre for Cancer Innovations at the Centenary Institute.

However, there are, of course, caveats.

“A significant portion do not respond to the vaccine in the first instance,” Dr Tiffen 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.”

Professor Christopher Sweeney, Director of the South Australian immunoGENomics Cancer Institute at Adelaide University said that while personalised vaccine marked a “step-change approach,” the trial population had quite specific characteristics.

“The study was conducted in patients who had no visible disease and a cancer ‘melanoma’ that is responsive to immune-enhancing drugs like pembrolizumab. Further research is needed to see if this approach is effective in patients who have cancer we can see and / or not responsive to the immune enhancer,” Professor Sweeney said.

Melanoma Institute Australia said the results will now enter a regulatory review process which may take several years, depending on the country. “Until then the treatment is not available.”

If and when the vaccine is approved, scaling it to reach patients throughout the community will also be challenging, says Associate Professor Seth Cheetham, Head of the Australian mRNA Cancer Vaccine Centre and Director of the National Biologics Facility at the University of Queensland.

“Each patient’s tumour must be sequenced, its neoantigens selected by an algorithm, and a bespoke mRNA manufactured and quality tested within weeks, so a commercial program will need tens of thousands of individual batches a year rather than a few large ones. Responsive manufacture will be essential in a country where someone is diagnosed with melanoma every 30 minutes,” Associate Professor Cheethman said.

The trial was funded by Merck Sharp & Dohme, a subsidiary of Merck & Co., and Moderna.