Personalized vaccine cuts melanoma recurrence after surgery

The INTerpath‑001 phase‑3 study, presented at the 2026 ESMO Congress, tested a personalized mRNA cancer vaccine called intismeran alongside the checkpoint inhibitor pembrolizumab. The patients had all had surgery for high‑risk melanoma. Adding intismeran cut the risk of recurrence or death by 42 % (hazard ratio 0.58; 95 % CI 0.45–0.75; p < 0.001). At two years, 82.2 % of patients on the combination were alive without recurrence, compared with 70.0 % on pembrolizumab alone.

Trial design and numbers

The trial enrolled 1,137 adults with stage IIB‑IV cutaneous melanoma. They were randomly assigned to pembrolizumab plus either intismeran (757 patients) or a placebo (380 patients). After a median follow‑up of 24.6 months, the combination also reduced the risk of distant metastasis or death by 38 % (HR 0.62; 95 % CI 0.45–0.85; p = 0.002). Overall survival data were still immature at this interim analysis, with no statistically significant difference between the groups (HR 0.77; 95 % CI 0.45–1.31), so longer follow‑up is needed.

Grade 3 or higher adverse events occurred in 23.6 % of patients on the combination and 20.3 % of those on pembrolizumab alone. The most common side effects with the vaccine were fever (52.2 % vs 8.2 %), injection‑site pain (51.0 % vs 9.5 %) and fatigue (38.5 % vs 29.7 %). Side effects linked to the injections were generally low grade and transient.

Lead author Dr Georgina Long said the study was the first phase 3 trial to show that a vaccine built from a patient’s tumour fingerprint can lower the risk of recurrence or death. “For a patient, more time free of melanoma is a meaningful benefit in its own right,” she said, adding that longer follow‑up is needed to show effects on melanoma‑specific and overall survival. Dr James Larkin, a scientific co‑chair of ESMO 2026 who was not involved in the study, said the reduction in relapse risk was clinically significant and the combination was very well tolerated. He said further trials are needed to establish whether the approach could benefit other cancers. Trials are already under way in lung, bladder and kidney cancer.