Moderna and Merck reported on Oct. 22 that a customized cancer vaccine for people with late-stage melanoma can reduce the risk of cancer recurrence or death over two years by 42% compared to current treatment.
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vaccine → report → treatment
The results will be presented at the European Society of Medical Oncology meeting in Madrid on Oct. 24.
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results → present → Oct.
The study involved more than 1,130 people with Stage 2B to Stage 4 melanoma, all of whom had their tumors surgically removed.
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tumors → involve → whom
Some were then randomly assigned to have a cancer vaccine custom-made after their tumors had been genetically sequenced.
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tumors → assign → vaccine
They received that vaccine, called intismeran, once every three weeks for up to nine doses, along with Keytruda, a checkpoint inhibitor, every six weeks for up to nine cycles, for about a year.
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They → receive → year
Others were randomly assigned to receive a placebo vaccine and Keytruda.
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.
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Intismeran → assign → 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.
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which → cod → 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.
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approach → use → 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.
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they → contribute → 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 a year.
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combination → surprise → year
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.
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cancer → report → inhibitor
“This Phase 3 [study] included a much broader population, so the hypothesis was that the treatment effect would be harder to see.
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effect → include → population
There was a lot of suspicion going in that these results would not be as good as those in the Phase 2.
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results → be → Phase
But the fact that they reproduced almost exactly what we saw initially in the Phase 2 blew my mind.”
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we → reproduce → mind
The companies report that the effect seems to start six months into the therapy—an important insight in understanding how immune-based approaches may work in cancer.
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approaches → report → cancer
“We think it’s because the immune system takes time to be activated,” says Berman.
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Berman → think → time
That includes making sure that immune cells like T cells, which are critical to recognizing and controlling cancer, have time to learn to detect tumors.
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which → include → tumors
Berman says these results could also help to explain why only about 30% of cancer patients respond to the checkpoint inhibitors, a powerful new tool in cancer that allows immune cells to see tumors rather than thinking they are "self" cells and therefore not foreign.
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they → say → tumors
“This shows us that in a significant percentage of patients, the checkpoint inhibitors are not doing anything because the immune system hasn’t even been educated to recognize the cancer cells,” he says of the potential role that the mRNA-based intismeran may play.
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intismeran → show → that
“That’s where we now need to focus—on how to better educate the immune system.
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we → ’ → system
It’s a big leap, a big piece of information, that there is now another way to educate the immune system to recognize cancer.
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It → ’ → cancer
Moderna and Merck are studying the intismeran-Keytruda pairing in other cancer types in nine other studies, such as pancreatic and gastric cancer, as well as in three late-stage trials of non-small cell lung cancer.
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Moderna → study → cancer
They are also exploring the role of using intismeran alone in an early study in lung cancer.
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They → explore → cancer
Traditionally, personalized therapies have not been practical as medical treatment because of their high cost and long timeline to develop.
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therapies → develop → cost
But Berman is confident that the bespoke process of making an individualized mRNA cancer vaccine for each patient is both scalable and potentially affordable.
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process → make → patient
“We have scaled down the technical footprint and have plans to scale up [the program] to look at different tumors,” he says.
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he → scale → tumors
“The nice thing about the [mRNA] system is that it’s purely enzymatic, so no cell cultures need to be grown.”
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cultures → ’ → system
Another advantage of using mRNA is its speed—scientists at Moderna can develop a customized vaccine based on a patient’s tumor within weeks—critical for any patient with cancer.
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scientists → use → cancer
The Aporia
