Moderna and Merck: mRNA vaccine succeeds in Phase 3 melanoma trial
▼ Summary
– Moderna and Merck announced their personalized mRNA cancer vaccine, combined with Keytruda, succeeded in a late-stage trial for melanoma patients.
– The Phase 3 trial involved 1,137 patients with surgically removed stage IIB–IV melanoma, randomized 2:1 to receive the vaccine plus Keytruda or Keytruda alone for about a year.
– The combination therapy significantly extended recurrence-free survival and distant metastasis-free survival, though specific data were not disclosed.
– Prior Phase 2 data showed a 49% reduction in recurrence or death risk and a 59% reduction in distant metastasis or death risk.
– The vaccine uses synthetic mRNA encoding up to 34 patient-specific cancer mutations, identified by comparing cancer and healthy cell genetic sequences.
Pharmaceutical heavyweights Moderna and Merck have announced that their experimental mRNA vaccine, designed to target a patient’s individual cancer mutations, achieved success in a late-stage clinical trial for melanoma. The vaccine, when paired with an existing immunotherapy, extended the time before patients saw their cancer return.
The Phase 3 study, which produced the promising results, enrolled 1,137 participants with stage IIB through IV melanoma whose tumors had been surgically excised before the trial began. Researchers randomized the patients in a 2-1 ratio, meaning two patients received the personalized vaccine, known as intismeran or mRNA-4157, alongside Merck’s established checkpoint inhibitor Keytruda, for every one patient who received Keytruda alone. Treatment lasted roughly one year for both groups, and the study was conducted as a double-blind, placebo-controlled trial, so neither participants nor medical staff knew which therapy was administered.
According to a planned interim analysis, the combination of the tailored vaccine and Keytruda significantly improved what investigators call recurrence-free survival (RFS), or the period a patient remains cancer-free after treatment. The regimen also lengthened distant metastasis-free survival (DMFS), which tracks the time before cancer reappears in a part of the body separate from its original site. Moderna and Merck characterized the improvements in both RFS and DMFS as both statistically significant and clinically meaningful, though they stopped short of providing specific figures. Full data is slated for presentation at a forthcoming international medical conference.
The companies did, however, point to earlier findings from a five-year Phase 2 trial, unveiled at a cancer research meeting in June, which showed a 49 percent drop in the risk of recurrence or death and a 59 percent reduction in the risk of distant metastasis or death.
The mechanism behind intismeran hinges on synthetic mRNA that encodes the unique genetic blueprint of up to 34 mutations found in a patient’s own malignant cells. To develop the vaccine, scientists compare the genetic makeup of cancerous tissue against healthy cells, then isolate cancer-specific mutations that could enable the immune system to distinguish between the two. This individualized approach, if validated, would mark a breakthrough for both mRNA technology and bespoke cancer therapies, offering a first success in each arena.
(Source: Ars Technica)
