Moderna and Merck report Phase 3 success for personalised mRNA melanoma vaccine

Pharmaceutical giants Moderna and Merck have announced that their personalised mRNA-based cancer vaccine, intismeran, has demonstrated efficacy in a Phase 3 clinical trial for melanoma. The late-stage study marks a significant milestone for the use of messenger RNA technology in oncology, moving beyond infectious disease applications to target individual tumour mutations.

The trial involved 1,137 patients with stage IIB to IV melanoma who had previously undergone surgical removal of the cancer. Participants were randomised in a two-to-one ratio to receive either the combination of the tailored mRNA vaccine and Merck’s established monoclonal antibody treatment, Keytruda, or Keytruda alone. The study was placebo-controlled and double-blind, ensuring that neither the clinicians nor the patients knew which regimen was being administered.

Moderna and Merck reported that the combination therapy significantly extended both recurrence-free survival and distant metastasis-free survival. While the companies described the results as statistically significant and clinically meaningful, they withheld specific numerical data, stating that detailed findings will be presented at an upcoming international medical conference.

The mechanism of intismeran, also known as mRNA-4157, relies on synthetic mRNA to target up to 34 unique mutations specific to a patient’s cancer cells. By comparing the genetic sequences of cancerous and healthy cells, the therapy identifies cancer-specific mutations. The vaccine delivers the genetic code for these mutations to healthy cells, which then produce protein fragments that are presented to the immune system as antigens, training it to attack the cancer.

Earlier data from a five-year Phase 2 trial, presented in June, indicated a 49 per cent reduction in the risk of recurrence or death and a 59 per cent reduction in the risk of distant metastasis or death. The companies now refer to the treatment as a “neoantigen therapy,” a terminology choice made to avoid the terms “mRNA” and “vaccine” in the face of political hostility from US Health Secretary Robert F. Kennedy Jr., who has cancelled federal grants for mRNA technology.

University of Oxford cancer expert Lennard Lee described the announcement as the first positive Phase 3 trial of an individualised neoantigen therapy. While noting the significance of the result, Lee cautioned that the magnitude of the benefit, subgroup analyses, and mature overall survival data remain to be seen. These details will be crucial for determining where the treatment fits within routine melanoma care.