mRNA vaccine/pembrolizumab combo reduces post-surgery melanoma recurrence, death risk

In a new study, adding an individualized mRNA-based vaccine to post-surgery pembrolizumab immunotherapy for high-risk melanoma reduced the risk of melanoma recurrence or death by 42% compared with pembrolizumab alone.

The findings were announced in a presentation at the ESMO (European Society for Medical Oncology) Congress 2026 in Madrid.

According to a press release from the Melanoma Institute Australia, positive results in melanoma suggest this personalized approach may enable new treatments for other cancers.

Intismeran is an mRNA-based individualized neoantigen therapy, a type of personalized therapeutic cancer vaccine. It is designed for each patient, based on their tumour's unique identity, to train and activate the immune system to recognize and fight that patient’s specific cancer.

Professor Georgina Long,  Medical Director at Melanoma Institute Australia (MIA) and Chair of Melanoma Medical Oncology and Translational Research at The University of Sydney, presented the results of the phase 3 INTerpath-001 clinical trial at the ESMO Congress 2026.

This clinical trial included 1,137 patients whose melanoma had been surgically removed, but who were at very high risk of recurrence (stage IIB to IV). These patients had not previously received any cancer drug treatment. The trial compared treatment with 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 cancer recurrence after surgery. Abnormal proteins, called neoantigens, are unique to each melanoma. The vaccine (also known as individualized neoantigen therapy) uses mRNA technology and helps the patient’s immune system identify tumour cells. Pembrolizumab then counters the tumour’s inhibition of the immune system. As a result, the cancer is less likely to recur or metastasize.

The trial showed combining intismeran with pembrolizumab treatment 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 to 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 to pembrolizumab alone.

Importantly, the vaccine did not increase the side effects of pembrolizumab. Treatment was generally well tolerated, with the vaccine causing transient low-grade side effects (injection site pain, headache, and chills in some patients).

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

The presented results will be published in the New England Journal of Medicine (NEJM).