Leaked data confirm Moderna-Merck cancer vaccine cuts melanoma recurrence by 42%

A personalized mRNA cancer vaccine cut the risk of melanoma recurring or killing patients by 42 percent in a large, randomized trial, according to detailed results that Moderna and Merck released Thursday after the data leaked online ahead of schedule. The figures, from the Phase 3 trial known as INTerpath-001, build on the companies' positive top-line announcement in August by providing the first detailed numbers, and mark the first time a cancer vaccine built from an individual patient's own tumor has shown a statistically significant benefit in a trial of more than 1,000 people.

The companies had planned to withhold the numbers until a formal presentation Saturday at the European Society for Medical Oncology's annual congress in Madrid. Screenshots of the results circulated on social media Thursday morning, and ESMO lifted its embargo and released the full data rather than let a partial, uncontrolled leak stand. Moderna's stock, which had more than tripled since the companies first announced a positive trial outcome in August, fell sharply on the news even though the results were broadly in line with, or slightly better than, what many analysts had modeled.

The numbers

The trial enrolled 1,137 patients with stage IIB through IV melanoma who had their tumors surgically removed and had not yet received systemic therapy. Patients were randomly assigned, two to one, to receive either the vaccine — known as intismeran autogene, or V940 — alongside Merck's immunotherapy Keytruda (pembrolizumab), or Keytruda alone for about a year.

At a median follow-up of 24.6 months, the combination reduced the risk of recurrence or death by 42 percent compared with Keytruda alone, a hazard ratio of 0.58 that was highly statistically significant. Two-year recurrence-free survival was 82.2 percent in the vaccine group versus 70.0 percent in the comparison group. On the trial's key secondary measure, distant metastasis-free survival, the combination cut the risk by 38 percent, with 88.5 percent of vaccinated patients free of distant spread at two years versus 80.2 percent on Keytruda alone. Overall survival data remain immature, though the companies said they have observed a favorable trend.

Side effects were more common with the vaccine added, including fever in just over half of patients and injection-site pain, but the companies said no new safety signals emerged. Patients who got the combination discontinued treatment for side effects somewhat more often than those on Keytruda alone.

How a leak forced an early release

The circumstances of Thursday's disclosure were unusual for an industry that normally controls the release of trial data down to the minute. Merck had told investors as early as October 13 that the INTerpath-001 results would be unveiled as a late-breaking abstract in ESMO's Presidential Symposium, the congress's showcase session for practice-changing research. A separate Moderna announcement had set the formal presentation for Saturday afternoon in Madrid, with an investor webcast to follow.

That plan unraveled Thursday when, according to STAT News, an oncology news outlet published some of the trial's data, breaking the conference's media embargo. ESMO responded by releasing the full abstract and lifting the embargo rather than let an incomplete account dominate. Wall Street reacted immediately. STAT reported Moderna shares fell 17.6 percent to $202.63; a separate analysis from Biopharma Dive put the decline at nearly 25 percent, while Merck's stock slipped only modestly. Analysts attributed the drop less to the substance of the data than to investor expectations that had run ahead of it.

"There appears to be a sell-the-news reaction playing out here," William Blair analyst Myles Minter said. RBC Capital Markets' Trung Huynh wrote that the results landed at the low end of what investors had hoped for and showed some falloff from the strength of the earlier mid-stage data, adding that "while approval seems likely, commercial success is far less certain." Other analysts were more positive; TD Cowen's Tyler Van Buren said the findings cleared the threshold physicians generally expect to call a treatment practice-changing in the adjuvant melanoma setting.

A different kind of vaccine

Intismeran autogene is not a vaccine in the conventional, preventive sense. It is manufactured individually for each patient from a sample of their own tumor, using sequencing to identify as many as 34 mutations unique to that cancer, called neoantigens, and then encoding them into an mRNA shot meant to train the immune system to recognize and attack any cells carrying those same mutations if the cancer tries to return. The approach uses the same messenger-RNA platform Moderna built for its Covid-19 vaccine, redirected toward a patient-specific target rather than a shared viral protein.

The companies' earlier, smaller study, a 157-patient Phase 2b trial called KEYNOTE-942, had shown an even larger benefit — roughly a 49 percent reduction in recurrence or death at longer follow-up — raising investor expectations that a trial eight times the size would reproduce similarly dramatic results. Phase 3 trials frequently show a smaller effect than earlier, smaller studies, and analysts said Thursday's data, while still substantial, illustrated that pattern.

Patients and what comes next

Melanoma specialists not involved in running the trial said the results were still clinically meaningful for patients facing a cancer with a high rate of recurrence after surgery. Janice Mehnert, an oncologist at NYU Grossman School of Medicine, said the outcomes "made a huge difference for the patients who got the vaccine," and Patrick Ott of Dana-Farber Cancer Institute, who has studied neoantigen vaccines for years, said he remained "a true believer" in the underlying mechanism. One trial participant, Ted Komenda, described the ongoing reassurance of clean follow-up scans and skin checks.

"So far, so good — they've come back clean."

Georgina Long, the trial's principal investigator, called the findings a potential turning point for how melanoma is treated after surgery, while cautioning that "longer follow-up is needed to show an impact on melanoma-specific and overall survival." Moderna chief executive Stéphane Bancel said the data reinforced his view that "mRNA has the potential to fundamentally change how we treat cancer."

Merck and Moderna said the full results have been accepted for publication in The New England Journal of Medicine and that they are now in discussions with regulators, without specifying a timeline for an application to the Food and Drug Administration. The formal presentation is still set for Saturday's Presidential Symposium, where lead investigator Long is scheduled to walk through the data in full. Intismeran is also being tested in nine other trials across several cancer types, including three Phase 3 studies in non-small cell lung cancer, which will determine how far beyond melanoma the approach can extend.