Personalised therapeutic cancer vaccine cuts risk of melanoma recurrence, opening door to new era of cancer treatment

Trial findings herald a foundational shift in how cancer is treated. Proven in melanoma, these results establish a new personalised approach, opening the door for potential new treatments for other cancers.

Intismeran is an mRNA-based individualised neoantigen therapy, a type of personalised therapeutic cancer vaccine. It 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.

Adding intismeran to pembrolizumab immunotherapy after surgery for high-risk melanoma reduced the risk of melanoma recurrence or death by 42% compared with pembrolizumab alone.

An entirely new type of cancer treatment, proven for the first time in a large international clinical trial, the highest standard of clinical evidence.

Two world firsts: the first mRNA cancer treatment, and the first individualised neoantigen therapy made from each patient’s own cancer, to be proven in a trial of this scale.

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, will present the results of the phase 3 INTerpath-001 clinical trial at the ESMO (European Society for Medical Oncology) Congress 2026.

“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.” – Professor Georgina Long

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). These patients had not previously received any cancer drug treatment. The trial compared treatment with a type of personalised therapeutic cancer vaccine, intismeran, given with pembrolizumab immunotherapy versus treatment with pembrolizumab alone.

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% reduction in risk

The phase 3 INTerpath-001 results are a landmark moment for cancer treatment. The trial showed adding intismeran to pembrolizumab reduced the risk of melanoma recurrence or death by 42% (hazard ratio [HR] 0.58; 95% confidence interval [CI] 0.45–0.75; p<0.001) 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% (HR 0.42) 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 (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. 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.” – Professor Georgina Long

How does this new treatment work?

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 Georgina Long

The vaccine helps the immune system to 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. Pembrolizumab blocks the handshake, allowing immune cells to recognise the cancer and attack it, but it is the same drug for everyone. The vaccine gives a patient’s immune cells a personalised wanted poster of their cancer, so the combination works in more patients.” – Professor Georgina Long

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.

An international trial

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.

Professor Georgina Long AO was the global Principal Investigator of this international trial and Chair of the Trial Steering Committee.

“This is the first phase 3 study to show that a treatment built from the unique ‘fingerprint’ of a patient’s own tumour can reduce the risk of recurrence or death from cancer. That fingerprint is read by sequencing the tumour, then a ‘wanted poster’ of the cancer is made as mRNA, showing the immune system exactly what to look for and attack. 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.” – Professor Georgina Long

Professor Matteo Carlino, medical oncologist and member of MIA faculty, led the trial at Westmead Hospital.

“It has been an incredible opportunity to be part of this Australian and international collaboration, contributing to the development of intismeran from its early phase development through to this groundbreaking trial. Intismeran has the potential to revolutionise the management of melanoma, and also multiple other types of cancer.” – Professor Matteo Carlino

Professor Alex Menzies, medical oncologist and senior researcher, and MIA’s medical oncology and clinical trials teams played a pivotal role in the trial’s success.

“This trial demonstrates that the addition of a personalised mRNA-based vaccine to current standard immunotherapy treatment leads to a major improvement in recurrence-free survival for those with high-risk, resected melanoma. The hope for the near future is that it may not only improve outcomes for melanoma patients with advanced disease, but also those with other types of cancer where current immunotherapies are poorly effective.” – Professor Alex Menzies

The 1137 patients who volunteered for this trial have helped change the future of cancer treatment for others.

Melanoma leading the way for new cancer treatments

Melanoma is Australia’s cancer. Australia has one of the highest melanoma rates in the world, with one person diagnosed every 30 minutes and one person dying every 6 hours from the disease. It is also the most common cancer in Australians aged 20 to 39.

Progress in melanoma treatment over the past decade has been extraordinary, driven by research led by Melanoma Institute Australia.

Fifteen years ago, survival after a stage IV advanced melanoma diagnosis, where the melanoma has spread to other parts of the body, was measured in months. Today nearly 55% of patients with advanced melanoma are effectively cured.

First came BRAF-targeted drug therapies, followed by checkpoint inhibitor immunotherapies, which harness the body’s own immune system to fight cancer. A recent ground-breaking advance was neoadjuvant immunotherapy, giving immunotherapy before surgery rather than after. Breakthroughs, such as immunotherapy, have transformed outcomes not only for melanoma, but also for cancers such as lung and kidney cancer.

What’s next?

These results now enter a regulatory review process which may take several years, depending on the country.

Until then the treatment is not available. Patients with melanoma who want to know more should talk to their medical oncologist.

Results will be published in the New England Journal of Medicine (NEJM).