Adding a personalized vaccine to Keytruda improved survival without cancer returning after surgery, the companies report from a 1,137-patient trial as they seek approval.
Merck and Moderna reported on October 22 that adding their personalized cancer vaccine, intismeran, to Keytruda reduced the risk of melanoma returning or death by 42% in a large randomized trial after surgery. On October 23, Oxford researcher Lennard Lee reported that the combination also caused treatment-related side effects in approximately six additional patients per 100, while severe-event rates were similar.
The companies had announced in August that the trial succeeded without releasing detailed results. The study tested whether adding the vaccine to Merck’s established cancer treatment improved outcomes after surgery to remove melanoma, a form of skin cancer.
In comments published by the Science Media Centre on October 23, Lee, an associate professor at the University of Oxford, said the additional side effects included fever, fatigue and injection-site reactions. He described the rates of severe treatment-related side effects as very similar between the vaccine combination and the control treatment. Keytruda is the brand name for pembrolizumab.
| Outcome | Intismeran plus Keytruda | Keytruda plus placebo |
|---|---|---|
| Patients with severe treatment-related side effects | 14.2% | 13.4% |
The partners are testing the personalized vaccine where Merck’s immunotherapy Keytruda has worked best, and are preparing to seek approval after a large melanoma trial.
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The Phase 3 trial—a late-stage study—enrolled 1,137 patients with stage IIB–IV melanoma that had been surgically removed. Researchers randomly assigned patients in a two-to-one ratio to receive intismeran plus Keytruda or Keytruda plus a placebo. The companies reported the following outcomes.
| Outcome | Intismeran plus Keytruda | Keytruda plus placebo |
|---|---|---|
| Alive without cancer returning at two years | 82% | 70% |
| Alive without cancer spreading to a distant part of the body at trial end | 88.5% | 80% |
The two-year figures represent a 12-percentage-point difference in the proportion alive without cancer returning. The reported 42% relative risk reduction compares the combined risk of recurrence or death between the groups; it does not mean deaths alone fell by 42%. The companies also reported a 38% relative reduction in the combined risk of cancer spreading to a distant part of the body or death.
Researchers compare the genetic sequences of a patient’s cancer cells with those of healthy cells and select cancer-specific mutations that could help the immune system target the cancer selectively. Intismeran uses synthetic messenger RNA, or mRNA, which carries genetic instructions encoding up to 34 mutations from that patient’s cancer.
Lee disclosed that he leads Oxford’s UK Cancer Vaccine AI Scientist & Supercomputing programme, funded by the Advanced Research and Invention Agency. He also disclosed past national advisory and leadership roles supporting cancer-vaccine research and clinical trials in the NHS, the UK health service, and the UK government, and said he designed and co-founded the NHS Cancer Vaccine Launch Pad.
In the same October 23 release, cancer-institute director Christopher Sweeney disclosed consulting payments from Merck, pembrolizumab’s manufacturer, and said he had no financial conflicts of interest with Moderna. The Science Media Centre said the other experts had not replied to its request for declarations of interests.
Lee said on October 23 that the full publication was still awaited and that researchers did not yet know whether the vaccine helped patients live longer. A reduction in the combined outcome of recurrence or death does not by itself establish an improvement in overall survival—how long patients live. The full results are also needed to assess the precision of benefit estimates, including confidence intervals, the ranges expressing statistical uncertainty.
The data were scheduled for presentation at an oncology conference on October 24 and had been accepted for publication in the New England Journal of Medicine. The vaccine remains unapproved, and Merck and Moderna are engaging with regulators to seek approval.
Update ·
Adds expert-reported side-effect figures, the benefit–harm tradeoff, declared interests and the pending question of whether the vaccine helps patients live longer.
