Personalized mRNA Vaccine Cuts Melanoma Recurrence Risk by 42%
In a phase 3 trial of 1,137 patients, intismeran plus pembrolizumab after surgery lowered the risk of recurrence or death. Survival data are not yet mature.
A personalized mRNA cancer vaccine given with immunotherapy after surgery for high-risk melanoma cut the risk of recurrence or death by 42%, according to phase 3 INTerpath-001 results presented at the ESMO Congress 2026. The vaccine, intismeran autogene, was given with pembrolizumab and compared with pembrolizumab alone.
Anti-PD-1 treatment such as pembrolizumab is a standard option after surgery, yet many patients relapse. Earlier phase 3 trials that added a second checkpoint inhibitor failed to improve on it. Intismeran works differently. Each patient's tumor is sequenced to find neoantigens, abnormal proteins specific to the cancer, and up to 34 of them are encoded in mRNA to help the immune system recognize any remaining cancer cells.
The numbers
The trial randomly assigned 1,137 adults who had surgery for stage IIB–IV cutaneous melanoma: 757 to pembrolizumab plus intismeran and 380 to pembrolizumab plus placebo. After a median follow-up of 24.6 months, the hazard ratio for recurrence or death was 0.58. At two years, 82.2% of patients on the combination were alive without recurrence, against 70.0% on pembrolizumab alone.
Risk of distant metastasis or death fell by 38%, with 88.5% versus 80.2% alive without distant spread at two years. Benefits were similar in lower- and higher-risk groups.
Overall survival data are still immature. At this interim analysis there was no statistically significant difference between the groups.
Side effects
Grade 3 or higher adverse events occurred in 23.6% of patients on the combination and 20.3% on pembrolizumab alone. The most common 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 tied to the injections were generally low grade and transient.
Lead author Dr. Georgina Long of Melanoma Institute Australia and the University of Sydney called it the first phase 3 study to show that a treatment built from the "fingerprint" of a patient's own tumor can reduce 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 an effect on survival.
Dr. James Larkin, scientific co-chair of the congress, who was not involved in the study, said the reduction in relapse risk is clinically significant and the combination is very well tolerated. Trials are already underway in lung, bladder and kidney cancer.
Source: Medical Xpress