Merck and Moderna are weighing where to push their combined mRNA cancer vaccine next, after a Phase 3 trial delivered what the companies describe as the first positive late-stage result ever recorded for an mRNA-based cancer therapy.
Speaking at a STAT Summit event in Boston this week, Moderna President Stephen Hoge and Merck's head of research and development, Dean Li, said the companies are now prioritizing which additional cancers to pursue with the regimen — a personalized vaccine called intismeran autogene, known in trials as mRNA-4157, paired with Merck's blockbuster immunotherapy Keytruda.
The trial results
In a Phase 3 interim readout announced in August, the combination met its main goal of reducing melanoma recurrence compared with Keytruda alone, and a secondary goal of slowing the cancer's spread to new parts of the body, in a trial of 1,137 patients with high-risk, surgically removed stage IIB-IV melanoma. The companies reported no new safety concerns. Full efficacy figures from the Phase 3 trial have not yet been released, but an earlier mid-stage study found patients on the combination were 44% less likely to have their cancer return or die than those on Keytruda alone — a figure that improved to 49% after three years of follow-up, according to the Irish Times. The same mid-stage data showed a 62% reduction in the risk of the cancer spreading or causing death.
What it means for both companies
The result matters most for Merck's long-term outlook: Keytruda, its top-selling drug, faces patent expiration later this decade, and the vaccine combination is seen as a candidate to help fill that gap. For Moderna, which has struggled since the pullback in Covid-19 vaccine demand, analysts view the melanoma program as central to a return to profitability. Moderna's shares jumped sharply, at one point more than doubling in pre-market trading, after August's announcement, and the stock had already more than doubled for the year before that news.
Hoge said the companies still have a lot of exploring to do in choosing where to test the vaccine next, according to a STAT News account of the Summit discussion. Li said the companies would move quickly to pivot toward any cancer type where a rival therapy showed positive data.
What's next
Melanoma remains the furthest along, with the companies preparing to seek regulatory approval — Moderna's chief executive has said clearance could arrive as early as 2027. Trials of the combination are also under way in adjuvant lung, kidney and bladder cancer, with smaller studies in pancreatic and gastric cancer. Each dose is manufactured individually: an algorithm scans a patient's tumor for up to 34 mutations to build a personalized vaccine, a process that takes about six weeks, during which patients continue taking Keytruda. Pricing and the logistics of manufacturing personalized treatments at scale remain open questions the companies have not yet addressed publicly.
