Moderna and Merck report 42% lower risk of melanoma recurrence or death with mRNA vaccine

Trial results

Moderna and Merck said Thursday their personalized mRNA vaccine against melanoma reduced the risk of death or recurrence by 42 percent compared with standard treatment in a late-stage trial. The partners said they are engaging with regulatory authorities to seek approval. The trial included 1,137 patients with stage IIB to IV melanoma that had been surgically removed before enrollment. Patients were randomized two to one to receive either a combination of the personalized mRNA vaccine and standard treatment or standard treatment alone. The standard treatment was Merck's Keytruda, a monoclonal antibody cancer treatment.

After two years, 82 percent of participants who received the vaccine combination were alive without recurrence, compared with 70 percent of those who received Keytruda and a placebo. The vaccine combination reduced the risk of distant metastasis or death by 38 percent. At the end of the trial, 88.5 percent of the combination group were alive without distant metastasis, compared with 80 percent of the Keytruda and placebo group.

How the vaccine works

The tailored vaccine, intismeran or mRNA-4157, uses synthetic mRNA carrying genetic coding for up to 34 mutations in a patient's own cancer cells. Researchers compare genetic sequences from cancer cells and healthy cells, then select cancer-specific mutations that could help the immune response target cancer cells selectively. Merck and Moderna said the approach reflects their belief that mRNA technology can support cancer treatments matched to each patient's tumor.

Earlier data and next steps

The partners reported in August that the vaccine had succeeded in the trial, but delayed detailed results until presentation at the European Society of Medical Oncology conference in Madrid, Spain. After an oncology news site reported results early and broke the embargo, the companies released top-line results; the full data has been accepted for publication in the New England Journal of Medicine. The Phase 3 findings were less strong than a five-year Phase 2 trial, which showed a 49 percent reduction in the risk of recurrence or death and a 59 percent reduction in the risk of distant metastasis or death. Dean Li, president of Merck Research Laboratories, called the trial the first Phase 3 study to show a clinically meaningful improvement in recurrence-free survival and distant metastasis-free survival over standard-of-care Keytruda in patients with resected melanoma.

Sources: Ars Technica