Personalized mRNA therapy intismeran plus pembrolizumab reduced the risk of recurrence or death after melanoma surgery by 42%

Personalized mRNA therapy intismeran plus pembrolizumab reduced the risk of recurrence or death after melanoma surgery by 42%

The phase III INTerpath-001 trial enrolled 1 137 people whose melanoma had been completely removed. All received pembrolizumab; one group also received intismeran, a therapy tailored to each patient's tumor, while the other received a placebo. The trial measured the added benefit of personalized mRNA therapy after surgery.

On October 22, Merck released detailed results from the trial. At a median follow-up of 24,6 months, the hazard ratio was 0,58: the risk of recurrence or death in the intismeran group was 42% lower than in the group receiving pembrolizumab alone. At two years, 82,2% of patients in the combination group and 70,0% in the control group remained free of recurrence.

The therapy is tailored to each patient's tumor. Sequences from the tumor and normal tissue are compared to select up to 34 neoantigens, protein fragments altered by mutations that the immune system can use to recognize cancer cells. These are then encoded in mRNA. Both groups received pembrolizumab, and the control group received a placebo in place of intismeran, so the difference between the groups reflects the benefit of adding the personalized therapy to the shared treatment regimen.

For the second endpoint, the risk of distant metastasis or death, the combination reduced the risk by 38%. At two years, 88,5% of patients in the combination group and 80,2% in the control group remained free of distant metastases.

The companies' August announcement reported only that the trial had met its prespecified objectives, without giving exact effect sizes. According to BioSpace, Moderna shares fell by 21% to $193,65 after the new figures leaked on October 22. Analysts compared the hazard ratio of 0,58 with the phase II result of 0,51 and with results from preoperative immunotherapy.