A personalised melanoma vaccine developed by Merck and Moderna cut the risk of recurrence or death by 42% when added to standard immunotherapy, according to detailed phase 3 results. The trial compared the vaccine plus Keytruda with Keytruda alone in patients whose stage IIB to IV melanoma had been completely removed by surgery. The therapy, intismeran autogene, remains investigational.

What the Phase 3 Trial Found

The INTerpath-001 trial randomised 1,137 patients in a 2:1 ratio to receive either the combination of intismeran and Keytruda or Keytruda with a placebo. The companies released detailed results on 22 October 2026, ahead of a presentation at the European Society for Medical Oncology congress in Madrid, after the figures emerged early because of an embargo breach. Keytruda is already used after surgery for certain patients with resected melanoma, so the comparison reflects current practice.

Key facts: after a median follow-up of 24.6 months, the hazard ratio for recurrence or death was 0.58. Two-year recurrence-free survival was 82.2% with the combination and 70.0% with Keytruda alone. Distant metastasis or death fell by 38%, with a hazard ratio of 0.62. Overall survival data remain immature.

The treatment is a personalised mRNA vaccine encoding up to 34 neoantigens, built around the mutations in each patient's own tumour. Georgina Long, the trial's principal investigator at Melanoma Institute Australia, said the findings support 'a fundamentally new and individualized approach' to treating resected melanoma. The results have been accepted for publication in The New England Journal of Medicine.

Why the Benefit Appeared After Six Months

The headline figure masks an uneven pattern. During the first six months, the combination performed much like Keytruda alone, with a hazard ratio of 0.99. After that point, a prespecified sensitivity analysis showed a 58% lower relative risk of recurrence or death with the combination compared with Keytruda alone.

Long explained that the vaccine needs time to prime the immune system and that intismeran was administered a median of 64 days after pembrolizumab treatment began. Investigators therefore planned analyses to account for the delayed onset.

Safety looked manageable. Grade 3 or higher adverse events, regardless of their attribution to treatment, occurred in 23.6% of patients receiving the combination and 20.3% receiving Keytruda with a placebo. Long said the vaccine did not amplify Keytruda's immune-related side effects, with its own toxicities being transient injection-site and vaccination-related reactions such as chills and fever.

Overall survival is the missing piece. The interim hazard ratio of 0.77 did not reach statistical significance, and longer follow-up is needed to show whether fewer recurrences translate into longer lives.

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Markets Cool on the Personalised Melanoma Vaccine

Investors were less impressed than the scientists. Moderna shares closed 17.6% lower on 22 October, despite the positive phase 3 results, following what analysts described as a 'sell-the-news' reaction. The decline came despite an earlier phase 2b trial reporting a 49% reduction in the risk of recurrence or death after five years of follow-up.

Comparing the two is imperfect, since that smaller study enrolled patients with resected stage IIIB to IV melanoma, whereas INTerpath-001 also included earlier-stage patients.

Merck and Moderna are engaging with regulatory authorities, and AFP reported in August that the therapy has received expedited regulatory designations from the US Food and Drug Administration and the European Medicines Agency. The companies are testing intismeran in nine phase 2 and phase 3 trials across melanoma, lung, bladder and kidney cancer.

Intismeran has not been approved for any use. Overall survival follow-up continues, and those figures will help determine how far the personalised melanoma vaccine travels beyond this trial.

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