Pharmaceutical partners Moderna and Merck announced on Wednesday that their novel mRNA-based vaccine—individually tailored to target a patient’s unique cancer mutations—was effective in a late-stage clinical trial of patients with melanoma, one of the deadliest forms of skin cancer.
The announcement was scant on details, but if the success holds, it stands to realize the high aspirations for both mRNA vaccines and individualized cancer-targeting medicines in cancer therapy, providing a first success for both treatment types.
The Phase 3 trial included 1,137 patients who had stage IIB–IV melanoma that had been surgically removed prior to their treatment in the trial. Patients were randomized 2-1 to receive either a combination treatment of the tailored mRNA vaccine (intismeran or mRNA-4157) with Merck’s established monoclonal antibody cancer treatment Keytruda, or they received treatment with Keytruda alone. Both patient groups were treated for about a year. The trial was placebo-controlled and double-blind, meaning neither the doctors nor the patients knew which treatment patients were randomly assigned to receive.
Based on a planned interim analysis, Moderna and Merck report that the combination therapy with the mRNA vaccine extended “recurrence-free survival” (RFS), which is the amount of time a patient has without the cancer returning. The combination therapy also extended “distant metastasis-free survival” (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.
The companies say the extensions of RFS and DMFS reported were statistically significant and clinically meaningful, but they did not elaborate. They said the data will be presented at an upcoming international medical conference. They did note, however, that data from a five-year Phase 2 trial, which was presented at a cancer researcher conference in June, 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.
The mRNA vaccine intismeran works using a synthetic mRNA that holds the unique genetic coding for up to 34 mutations in a patient’s own cancer cells. The production process involves comparing the genetic sequences of a patient’s cancer cells to those of healthy cells and picking out any cancer-specific mutations that could help the immune system differentiate cancer cells from healthy ones.
Using the same platform Moderna used for its mRNA COVID-19 vaccine, intismeran delivers to healthy cells the mRNA code for those mutations. Healthy cells translate that mRNA code into protein fragments representing the cancer mutations, and then those fragments are presented to immune cells as antigens, a foreign substance to attack. As such, Moderna and Merck call their mRNA cancer vaccine a type of “neoantigen therapy.”
The term avoids both “mRNA” and “vaccine,” which draw hostility from Trump’s anti-vaccine Health Secretary Robert F. Kennedy Jr. In addition to his concerted efforts to undermine lifesaving vaccines, Kennedy has canceled hundreds of millions of dollars in federal grants for the development of mRNA vaccine technology.
In the companies’ announcement, Georgina Long, who led the trial, said the results were “a landmark moment” with the “potential to establish a new treatment paradigm.” Dean Li, president of Merck Research Laboratories, said the findings “reinforce the promise of a more personalized approach to cancer treatment.” Moderna CEO Stéphane Bancel, meanwhile, highlighted mRNA technology’s role, saying this is “a pivotal moment for the field of cancer research.”
“For many years, the idea of creating an mRNA treatment designed specifically for an individual patient’s cancer was aspirational. We are now helping turn that vision into a reality,” Bancel said.
Despite the lack of details, outside experts are similarly hopeful and encouraged by the announcement. “This is the first positive Phase III trial of an individualized neoantigen therapy and an mRNA-based cancer treatment,” University of Oxford cancer expert Lennard Lee said in a statement. “That makes this an important moment for a field that scientists have been working towards for many years. Within six years of the pandemic, we have mRNA vaccines to treat cancer,” he said, also calling it “very encouraging” and “significant.”
Lee, however, highlighted that we don’t yet know the magnitude of the benefit, the detailed subgroup analyses, quality-of-life data, or mature overall-survival results. “Those details will allow the scientific and clinical community to understand precisely how large the benefit is, which patients benefit most, and ultimately where this treatment might sit within routine melanoma care,” he said.
