Science1 publisher2 min readPublished
Merck and Moderna's melanoma result leaves the next target for mRNA cancer vaccines unsettled
Merck and Moderna's mRNA vaccine intismeran autogene slowed the return and spread of melanoma when added to an existing treatment in a late-stage trial. One trial cannot say which other cancers the same approach can treat.
The Scientist · Science desk
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What happened
- The idea of using messenger RNA to train the immune system to attack cancer cells was first devised decades ago.
- According to STAT, the melanoma result suggested that this decades-old idea is now ready for further drug development.
- STAT reports that results across cancer vaccine trials have diverged, and the field is grappling with hard questions about them.
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Why it matters
- constraint A positive add-on trial in melanoma supports the vaccine plus standard treatment in that disease only, so any other cancer needs its own controlled trial before benefit can be claimed.
- decision Sponsors choosing the next tumor type to test must pick while results across cancer vaccine trials point in different directions and no rule yet predicts which cancers respond.
- cost Each additional cancer means another late-stage trial, so sponsors pay for evidence one tumor at a time before learning whether the melanoma effect carries over.
The late-stage melanoma trial was an add-on design: the vaccine was given on top of an existing treatment [1][3]. An add-on comparison is built so that any difference in how often the cancer comes back can be credited to the vaccine. It also limits the finding to that combination, in melanoma, as Merck and Moderna reported it in August [1].
The STAT account does not include the size of the effect or name the vaccine trials behind the divergent results in its headline [9]. Effect size is the first number I would ask for. A large drop in recurrence in a big trial is a stronger base for testing a second cancer than a small drop in a small one.
Karen Knudsen, chief executive of the Parker Institute for Cancer Immunotherapy, a research group that tech entrepreneur Sean Parker founded, said the field had been waiting "with bated breath" for the news on the drug [4][5]. That wait ended with one readout in one disease [1].
STAT frames the open problem as two questions. The second, whether mRNA is up to the task, is the one melanoma data cannot settle [8]. A negative trial in another cancer could reflect that tumor, or it could reflect a limit of the mRNA platform. Separating the two takes controlled trials in several cancers, each with a comparison as clean as the melanoma study's. In my view the August result justifies running those trials. It does not yet support a claim about any cancer other than melanoma [1].
What to watch
- Full publication of the melanoma trial data, with the effect size, patient numbers and follow-up time.
- Late-stage readouts of mRNA cancer vaccines in tumor types other than melanoma, especially any built on the same add-on design.
- Identification of which cancer vaccine trials produced the divergent results STAT describes, and how their designs differed.