Moderna and Merck report five-year durability for personalized mRNA melanoma therapy, sharpening focus on oncology and pandemic-readiness

Moderna and Merck (known as MSD outside the U.S. and Canada) used the 2026 ASCO Annual Meeting to extend a key oncology announcement, reporting five-year follow-up data for intismeran autogene, a personalized mRNA therapy designed to target each patient’s tumor neoantigens, given with Merck’s Keytruda (pembrolizumab). The companies said the combination continued to reduce the risk of recurrence or death in patients with high-risk stage III/IV melanoma who had undergone complete surgical resection.

The update comes from the Phase 2b KEYNOTE-942/mRNA-4157-P201 study. Moderna and Merck reported a median planned follow-up of 60.3 months (range 50.5 to 76.4). In the pre-specified analysis, they said intismeran autogene plus Keytruda reduced the risk of recurrence or death by 49% compared with Keytruda alone, with a hazard ratio of 0.51 (95% confidence interval 0.294 to 0.887).

They also reported continued benefit on a key secondary endpoint. For distant metastasis-free survival, the companies said the combination reduced the risk of distant metastasis or death by 59% versus Keytruda alone (hazard ratio 0.411; 95% CI 0.200 to 0.843). Overall survival was described as an exploratory endpoint with an encouraging trend (hazard ratio 0.471; 95% CI 0.165 to 1.345; n=14), but the companies did not characterize it as definitive.

Intismeran autogene is an investigational individualized neoantigen therapy, delivered as synthetic mRNA intended to code for up to 34 neoantigens based on a patient’s mutational signature. In the Phase 2b study, patients received intismeran autogene in addition to Keytruda, with the trial aimed at the adjuvant setting, where the goal is to prevent recurrence after surgery.

On safety, Moderna and Merck said the overall profile in this five-year update remained consistent with earlier analyses. They reported that the most common adverse events attributed to the combination included fatigue (59.6%), injection site pain (59.6%), and chills (51.0%). They said grade 3 fatigue was the most common grade 3 event (4.8%), with no grade 4-5 events reported in the intismeran autogene attribution category. Immune-related adverse events occurred in 45.2% of patients receiving the combination and 44% of patients receiving Keytruda alone.

For investors, the emphasis is not only the magnitude of the effect, but the durability. The five-year framing matters because adjuvant cancer therapies are judged by how long protection lasts after treatment ends, and personalized mRNA approaches are still building the case that customization can translate into repeatable clinical outcomes. Moderna, for its part, said the longer-term melanoma data add to confidence in the “durability” of the personalized approach made possible by mRNA technology.

At the same time, Moderna’s platform push extends beyond oncology. In December 2025, the company disclosed that the Coalition for Epidemic Preparedness Innovations (CEPI) will invest up to $54.3 million to support a pivotal Phase 3 clinical trial intended to help advance Moderna’s investigational H5 pandemic influenza vaccine candidate, mRNA-1018, to licensure, with the Phase 3 trial expected to begin in early 2026. CEPI’s agreement also includes Moderna’s commitment to allocate 20% of manufacturing capacity for the H5 candidate for timely supply to low- and middle-income countries at affordable pricing if the vaccine is licensed.

Still, important uncertainties remain. Moderna and Merck’s melanoma results include an exploratory overall survival announcement that depends on additional follow-up and event accumulation, and intismeran autogene remains investigational with no current regulatory outcome disclosed in the companies’ announcements. The companies also did not provide a detailed breakdown in the press materials on how individual subgroup outcomes differed beyond saying improvements were maintained across various categories. What to watch next is the publication in ASCO’s Journal of Clinical Oncology and updates tied to Moderna and Merck’s ongoing intismeran autogene development plans, including Phase 3 studies they said are fully enrolled or enrolling across melanoma and other tumor types. In parallel, investors will likely track progress on the planned early-2026 start for the mRNA-1018 Phase 3 program as a barometer of whether Moderna can broaden demand for mRNA beyond cancer and COVID-era vaccines.