Personalized mRNA vaccines against melanoma—the deadliest form of skin cancer—reduced the risk of death or recurrence by 42 percent compared to standard treatment in a late-stage trial, pharmaceutical partners Merck and Moderna announced Thursday.

The results are a significant advance in melanoma treatment; Merck and Moderna are already engaging with regulatory authorities to get the vaccine approved. More broadly, the vaccine’s success bolsters hope that mRNA vaccines and individualized cancer-targeting medicines offer a new paradigm for cancer therapies.

“From the beginning, we believed mRNA technology could make it possible to develop cancer treatments uniquely matched to each patient’s tumor,” Moderna CEO Stéphane Bancel said in a statement. The trial results “mark a defining moment for that vision and show what’s possible when we rethink how medicines are made.” They also “reinforce our conviction that mRNA has the potential to fundamentally change how we treat cancer,” he said.

In August, Moderna and Merck reported that the vaccine has succeeded in the trial, but held off reporting details until the data could be presented at an upcoming scientific conference. That conference is the European Society of Medical Oncology, starting now in Madrid, Spain. The data was scheduled for presentation on Saturday, but after an oncology news site reported the results early, breaking the embargo, the companies released the top-line results. The full data has been accepted for publication in the New England Journal of Medicine.

As Ars reported earlier, the Phase 3 trial included 1,137 patients who had stage IIB–IV melanoma that had been surgically removed prior to entering the trial. Patients were randomized 2-1 to receive either a combination treatment including the personalized mRNA vaccine with a standard treatment, or the standard treatment alone. The standard treatment was Merck’s established monoclonal antibody cancer treatment Keytruda.

New data

The tailored mRNA vaccine is intismeran (or mRNA-4157), which uses a synthetic mRNA that holds the unique genetic coding for up to 34 mutations in a patient’s own cancer cells. To produce the personalized vaccines, researchers compare the genetic sequences of a patient’s cancer cells with those of healthy cells and pick out cancer-specific mutations that could help the immune response selectively target just the cancer cells.

In the trial, researchers assessed “recurrence-free survival” or RFS, which is the amount of time a patient has without the cancer returning, and “distant metastasis-free survival” or DMFS, which is the amount of time a patient has without the cancer returning and occurring in a different part of the body than where it began.

According to the rushed-out press release, after two years, participants in the trial who received the intismeran-Keytruda treatment had 42 percent reduction in their risk of recurrence or death compared to the participants who just got Keytruda and a placebo. What that looked like after two years was that 82 percent of the intismeran-Keytruda treatment group were still alive without recurrence, while only 70 percent of the Keytruda-placebo group were alive without recurrence.

For distant metastasis-free survival, intismeran-Keytruda treatment reduced the risk of distant metastasis or death by 38 percent compared with the Keytruda-placebo group. At the end of the trial, 88.5 percent of the intismeran-Keytruda treatment group were alive without distant metastasis, while 80 percent of the Keytruda-placebo group were alive without distant metastasis.

The treatment effect was not as strong as seen in 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.

Still, the findings are an exciting advance for melanoma patients. The trial “is the first Phase 3 study to demonstrate a clinically meaningful improvement in RFS and DMFS over standard-of-care KEYTRUDA in patients with resected melanoma, setting a new benchmark in the adjuvant setting and representing one of the most significant advances in melanoma treatment since the advent of immunotherapy,” Dean Li, president of Merck Research Laboratories, said in an announcement.