In a world-first international trial, adding a type of personalised therapeutic cancer vaccine made from an individual patient’s own tumours to immunotherapy after surgery for high-risk melanoma, reduced the risk of recurrence or death by 42 percent.

Australia has one of the highest melanoma rates in the world, with one person diagnosed every 30 minutes. Research led by Melanoma Institute Australia (MIA) has transformed treatment, with nearly 55 per cent of patients with advanced melanoma now effectively cured.

Professor Georgina Long AO, Medical Director at Melanoma Institute Australia and Chair of Melanoma Medical Oncology and Translational Research in The University of Sydney’s Faculty of Medicine and Health and Charles Perkins Centre, will present the results of the phase 3 INTerpath-001 clinical trial at the ESMO (European Society for Medical Oncology) Congress 2026 this weekend.

Professor Long, Global Principal Investigator of the trial and Chair of the Trial Steering Committee, said: “These findings are a foundational shift in our approach to cancer: harnessing 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. It is the coming together of technology, our biological understanding of cancer and the immune system – and the courage to take this idea into the clinic.

“Having succeeded in melanoma, this proof of concept could mark the beginning of a foundational shift in how we treat cancer, helping patients remain cancer-free for longer.”

This clinical trial included 1137 patients whose melanoma had been surgically removed, but who were at very high risk of it returning (stage IIB to IV), and who had not previously received any cancer drug treatment.

Unlike a traditional vaccine that prevents disease in healthy people, intismeran is a therapeutic vaccine, designed for people after a cancer diagnosis who are at high risk of the cancer returning after surgery. It helps the immune system find and kill melanoma cancer cells, so the cancer is less likely to return or to spread to an advanced stage.

A melanoma is considered high risk if it has invaded a deeper layer of skin, has spread to nearby tissue and structures such as lymph nodes, or has metastasised to other areas of the body such as organs.

A 42 percent reduction in risk

The trial showed adding intismeranto pembrolizumab,  a type of immunotherapy,reduced the risk of melanoma recurrence or death by 42 percent, 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 – 58 percent – compared with pembrolizumab alone.

Importantly, pembrolizumab side effects were not increased by the vaccine. Treatment was generally well tolerated in patients, with the vaccine causing transient low grade side effects, such as injection site pain, headache, and chills in some patients.

“These results showed that patients with earlier-stage melanoma can be treated after surgery in a fundamentally new way. But these results are more than a landmark for melanoma – they mark a foundational shift for cancer medicine,” said Professor Long.

“The INTerpath-001 trial shows that treatment built from the unique signature of a patient’s own tumour, working alongside checkpoint inhibitor immunotherapy, can sharpen the immune system to find and destroy any remaining cancer cells.

“Just as email transformed how we communicate, individualised neoantigen therapy has the potential to transform how we treat cancer.”

How does the new treatment work?

Like a fingerprint, abnormal proteins, called neoantigens, give every melanoma its own unique identity. 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,” said Professor Long.

The vaccine helps the immune system identify the individual patient’s tumour cells. Meanwhile pembrolizumab releases the brakes the tumour places on immune cells.

“Cancer can fool the immune system with a fake friendly handshake, so the immune system thinks the cancer cell is normal,” said Professor Long.

“Pembrolizumab blocks the handshake, allowing immune cells to recognise the cancer and attack it, but it is the same drug for everyone, so the combination works in more patients.”

How the trial worked 

The INTerpath-001 phase 3 clinical trial was an international trial across 157 sites around the world. This included several Australian centres: Melanoma Institute Australia, Westmead Hospital NSW, One Clinical Research WA, Princess Alexandra Hospital QLD, Paula Fox Melanoma & Cancer Centre VIC, and Peter MacCallum Cancer Centre (Parkville Cancer Clinical Trials Unit) VIC.

The investigational mRNA-based individualised neoantigen therapy (also known as intismeran autogene, intismeran, V940, mRNA-4157, or personalised therapeutic cancer vaccine) is being jointly developed by MSD (tradename of Merck & Co) and Moderna, and is used in combination with MSD’s anti-PD-1 checkpoint inhibitor immunotherapy pembrolizumab.

For the full release and more details on how the trial worked, visit the Melanoma Institute of Australia.

Declaration and research information: 

The results will be presented on 24 October at the European Society for Medical Oncology Congress 2026 and will be published in the New England Journal of Medicine.

The INTerpath-001 trial was funded by Merck Sharp & Dohme, a subsidiary of Merck & Co, and Moderna.

The trial results will now undergo regulatory review, a process that may take several years, depending on the country. The treatment will not be available until regulatory approval relevant to each national jurisdiction is granted. Patients with melanoma who wish to learn more should speak with their medical oncologist. 

Image:

Professor Georgina Long AO, photographed by Tim Bauer. Republished with permission.