Intismeran, developed jointly by Moderna and Merck, represents a new way to harness the immune system in cancer, by training immune cells to recognize 34 specific proteins on tumor cells. The mRNA coding for these proteins, or antigens, are encased in a lipid particle in a similar way to Moderna’s COVID vaccine, which used mRNA from the COVID virus’ spike protein. Using this mRNA approach, once cells start making the foreign proteins coded for by the mRNA, the immune system sees them as intruders and mounts a response against them—and the latest data show that the approach works not just against viral proteins but also against those found on tumors.

Keytruda contributes a key part of the response by removing the brakes that keep immune cells from recognizing and attacking tumor cells because they originate from normal "self" cells.

“I was surprised by the fact that the results replicated the Phase 2 [study] so closely,” says Dr. David Berman, chief development officer at Moderna, referring to an earlier stage study the companies released in June that the combination lowered the risk of cancer returning or death by 49% over five years. That study also reported that the therapy lowered the risk of the cancer spreading to other sites by 59% compared to the checkpoint inhibitor alone. “This Phase 3 [study] included a much broader population, so the hypothesis was that the treatment effect would be harder to see. There was a lot of suspicion going in that these results would not be as good as those in the Phase 2. But the fact that they reproduced almost exactly what we saw initially in the Phase 2 blew my mind.”