Lugano/Madrid, 24 October 2026 – Adding a personalised mRNA-based cancer vaccine to immunotherapy after surgery for high-risk melanoma reduced the risk of recurrence or death by 42%, according to results from the phase 3 INTerpath-001 trial presented at the ESMO Congress 2026. (1) The vaccine, intismeran autogene, was given alongside pembrolizumab and compared with pembrolizumab alone.
Anti-PD-1 immunotherapy, such as pembrolizumab, is a standard treatment after surgery for high-risk melanoma, yet many patients still experience recurrence. Previous phase 3 trials adding a second checkpoint inhibitor failed to improve on anti-PD-1 treatment alone. (2,3,4) Intismeran takes a different approach, with each patient’s tumour being 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.
The trial randomly assigned 1,137 adults who had undergone surgery for stage IIB–IV cutaneous melanoma to pembrolizumab plus either intismeran (757 patients) or placebo (380 patients).
After a median follow-up of 24.6 months, adding intismeran reduced the risk of recurrence or death (hazard ratio [HR] 0.58; 95% confidence interval [CI] 0.45–0.75; p<0.001). At two years, 82.2% of patients receiving the combination were alive without recurrence, compared with 70.0% receiving pembrolizumab alone. 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), with 88.5% versus 80.2% alive without distant metastasis at two years. Benefits were similar across lower- and higher-risk disease groups. 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), and longer follow-up is needed to determine whether the reduction in recurrence translates into a survival benefit.
Grade 3 or higher adverse events occurred in 23.6% of patients receiving the combination and 20.3% receiving pembrolizumab alone. The most common side effects with the combination were fever (52.2% versus 8.2%), injection-site pain (51.0% versus 9.5%) and fatigue (38.5% versus 29.7%). Side effects associated with intismeran injections were generally low grade and transient.
“This is the first phase 3 study to show that a treatment built from the unique ‘fingerprint’ of a patient’s own tumour can reduce the risk of recurrence or death from cancer,” said lead author Dr Georgina Long, Melanoma Institute Australia and The University of Sydney, Australia. “That fingerprint is read by sequencing the tumour, then a ‘wanted poster’ of the cancer is made as mRNA, showing the immune system exactly what to look for and attack.”
Long also emphasised the significance of the findings for patients, while acknowledging the need for longer-term evidence. “For a patient, more time free of melanoma is a meaningful benefit in its own right,” she said. “Longer follow-up is needed 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 data from INTerpath-001 represent a major advance for the adjuvant treatment of stage II and III melanoma; the reduction in risk of relapse is clinically significant and, from the perspective of side effects, intismeran in combination with pembrolizumab is very well tolerated,” said Dr James Larkin, Scientific Co-Chair of the ESMO Congress 2026, who was not involved in the study.
Looking ahead, Larkin highlighted the need for further trials to establish whether this approach could benefit patients with other cancers. Trials are already under way in lung, bladder and kidney cancer. Larkin also emphasised the distinction between treating existing cancer and preventing cancer from developing: “This is very different from vaccinating individuals without cancer to reduce the risk of subsequent cancer development.”
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