The Vial From the Tumour
A personalised mRNA vaccine added to pembrolizumab cut melanoma recurrence or death by 42 percent in a phase 3 trial of 1,137 people. Overall survival is not yet shown.
A vaccine built from one melanoma kept more people clear. It has not yet shown they lived longer.
Intismeran autogene is a vaccine made from the mutations in one person's removed melanoma. It is also called V940 and mRNA-4157. Merck and Moderna gave it with pembrolizumab, the immunotherapy already used after surgery, and compared that pair with pembrolizumab plus a placebo.
The phase 3 trial, INTerpath-001, randomised 1,137 adults with completely resected stage IIB to IV cutaneous melanoma, across 157 centres. None had had systemic therapy before. At a median follow-up of 24.6 months, with data cut off on 30 June 2026, adding the vaccine cut the risk of the cancer coming back or the patient dying by 42 percent. The hazard ratio was 0.58, the 95 percent confidence interval 0.45 to 0.75, and the two-sided p-value was under 0.001.
At two years, 82.2 percent of the combination group were alive without recurrence. On pembrolizumab alone, 70.0 percent were. The risk of distant metastasis or death fell 38 percent (hazard ratio 0.62, p=0.002). At two years, 88.5 percent versus 80.2 percent were free of distant spread.
Overall survival is not there. The interim hazard ratio was 0.77, confidence interval 0.45 to 1.31, p=0.33. It missed the boundary the trial set in advance. Georgina V. Long of the Melanoma Institute Australia presented the full set at the European Society for Medical Oncology meeting in Madrid on 24 October 2026.
Of 1,749 patients screened, 302 were turned away because the tumour sample was not good enough to build a vaccine. For the people who were randomised to the combination, the company manufactured a vaccine more than 99 percent of the time. Merck and Moderna said the paper is accepted at the New England Journal of Medicine and that they are talking to regulators. A 2027 launch is the company's hope, not an approval.
This is not a shot that stops melanoma starting. It is a shot for people whose tumour has already been cut out, built from that tumour, added to a drug they might have received anyway.
Key Facts
- 1,137 adults, resected stage IIB–IV cutaneous melanoma, no prior systemic therapy
- About two to one: intismeran plus pembrolizumab versus placebo plus pembrolizumab
- Recurrence or death: hazard ratio 0.58, 42 percent relative reduction, p<0.001
- Two-year recurrence-free survival: 82.2 percent versus 70.0 percent
- Distant metastasis or death: hazard ratio 0.62, 38 percent relative reduction
- Overall survival immature: hazard ratio 0.77, p=0.33
- 302 of 1,749 screened excluded for an inadequate tumour sample
- Presented 24 October 2026, ESMO, Madrid, by Georgina V. Long
Why This Matters
Checkpoint drugs already keep some melanomas away after surgery. This is the first phase 3 evidence that a vaccine built from the patient's own mutations, added on top, keeps more of them away. The gap between 70 percent and 82 percent at two years is people, not a slogan. The question the trial has not answered is whether those people live longer.
What We Don't Know Yet
Overall survival. Median recurrence-free survival was not reached in either arm, so the curves can still move. The result is in people whose tumours could be sequenced after surgery. It says nothing about other cancers, and nothing about preventing a first melanoma. A filing is not an approval.