Personalised melanoma vaccine cuts risk of recurrence

Adding a personalised, mRNA-based cancer vaccine to standard immunotherapy after surgery for high-risk melanoma reduces the risk of recurrence or death by 42%. That’s according to the results of a breakthrough international trial, recently presented at the ESMO Congress 2026 by principal investigator Professor Georgina Long AO.

Designed for people who are at high risk of cancer recurrence following melanoma removal, the therapeutic cancer vaccine known as intismeran 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. The vaccine is being jointly developed by Merck and Moderna, and is used in combination with pembrolizumab — Merck’s anti-PD-1 checkpoint inhibitor immunotherapy.

Anti-PD-1 immunotherapy is a standard treatment after surgery for high-risk melanoma, yet many patients still experience recurrence. With intismeran, each patient’s tumour is sequenced to identify neoantigens — abnormal proteins specific to their cancer. Up to 34 neoantigens are encoded in mRNA to help the immune system recognise and attack any remaining cancer cells.

“We analyse a sample of each patient’s tumour to read its unique neoantigen fingerprint, then create a ‘wanted poster’ of the cancer,” explained Long, who is Medical Director at Melanoma Institute Australia and Chair of Melanoma Medical Oncology and Translational Research at The University of Sydney. “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.

“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.”

The phase 3 INTerpath-001 trial, conducted across 157 sites around the world, included 1137 patients whose melanoma had been surgically removed but who were at high risk of it returning (stage IIB to IV). These patients had not previously received any cancer drug treatment. The trial compared treatment with intismeran given with pembrolizumab versus treatment with pembrolizumab alone.

The trial showed that, two years after treatment commenced, the addition of 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. Importantly, pembrolizumab side effects were not increased by the vaccine and treatment was generally well tolerated.

Long said the results could mark the beginning of a foundational shift in how we treat cancer, with trials already underway in lung, bladder and kidney cancer. She did however acknowledge the need for longer-term follow-up “to show an impact on melanoma-specific and overall survival, as well as whether the early benefit we are seeing across stages and subgroups holds, and which patients benefit most”.

The results now enter a regulatory review process which may take several years, depending on the country. They will also be published in The New England Journal of Medicine.

Image credit: iStock.com/Alena Butusava