Moderna and Merck’s mRNA Cancer Vaccine Impresses but Experts Urge Caution

Pictured: A Moderna office building/hapabapa/iStock

Messenger RNA (mRNA) vaccines have arguably saved millions of lives since the start of the COVID-19 pandemic. In a recent interview with The Guardian, Moderna CMO Paul Burton indicated the same would be true for cancer and that his company could have these vaccines ready by the end of this decade.

Certainly, experts agree that COVID-19 highlighted the potential of mRNA in other areas like cancer and heart disease. But can Moderna—and science as a whole—realize this potential in as few as five years, as Burton told The Guardian?

At the 2023 American Association for Cancer Research's annual meeting, Moderna and Merck presented data from the Phase II trial of their therapeutic vaccine mRNA-4157/V940, in combination with Keytruda (pembrolizumab), for high-risk melanoma following complete resection. Compared with Keytruda alone, the combination led to a 44% reduction in the risk of recurrence or death. Over 12 months of observation, the recurrence-free survival rate was 83.4%, which dropped slightly to 78.6% over 18 months.

It was the first randomized, controlled trial to show benefit from this type of cancer vaccine, Jeffrey Weber, deputy director of NYU Langone’s Perlmutter Cancer Center and the study’s senior investigator, told NBC News on Sunday. These vaccines are designed with mRNAs encoding tumor-specific antigens that teach the immune system to kill the cancer cells that contain them.

Burton told The Guardian he believes Moderna will be able to offer personalized cancer vaccines against multiple different tumor types. The Boston-based biotech currently has four other mRNA vaccines, each currently in Phase I studies. This begs the question, just how quickly can Moderna get them across the finish line?

Despite the positive data, Moderna’s stock took an 8.4% hit on Monday after analysts said the road to regulatory approval for the mRNA-4157/V940-Keytruda combo would likely not include accelerated approval. SVB Securities analyst Mani Foroohar said in a note to clients that accelerated approval for adjuvant treatments is rare and that the data presented by Merck and Moderna was not likely to break this precedent.  

Cancer Vaccines: The Concept

Nested in pipelines belonging to Moderna, BioNTech and more, mRNA vaccines have long been envisioned for cancer. By targeting tumor-associated antigens, called neoantigens, these therapies can wipe out cancer cells while leaving healthy tissue untouched.

“The spectrum of mutations is really fairly unique for an individual patient, so if you’re going to make a vaccine, it’s probably best to do it in an individualized way, which is what we’ve done here,” Eric Rubin, senior vice president of clinical oncology at Merck, told BioSpace.

He emphasized the importance of testing the neoantigen therapy against early-stage cancer, as opposed to a cancer that has metastasized.

“I think it was very important and may underlie why so many prior trials of cancer vaccines have failed,” he said, adding that most of these have been in the metastatic setting. “If this study had been done in a metastatic setting, it might not have been positive.”

Catching the cancer at this stage may prevent it from ever reaching the metastatic stage, he said.

Gerald Linette, oncologist and professor of medicine at the Perelman School of Medicine, University of Pennsylvania who was not involved in the trial, agreed, saying that patients with bulky metastatic disease are not the best candidates for cancer vaccines due to immunosuppression. At this point, a person’s immune system is compromised and may not respond to the vaccine as well.

However, Linette noted that Moderna and Merck did not present any immune monitoring data. “We don’t really have a sense of the quality or the quantity or the magnitude of the immune response . . . . We have to understand that in order to kind of connect the dots and show causality in terms of the vaccine.”

Linette noted that for these vaccines to succeed, researchers would need to identify the ideal neoantigens to target cancer cells.

“The selection of the best antigens is really not well understood at this point,” he said.

Moderna and Merck have stated their intention to also study their mRNA-4157/V940-Keytruda combo in non-small cell lung cancer.

“Given the way it works, the biology and the interaction with Keytruda, there’s really no reason to think this would be limited only to melanoma,” Rubin said. “Some cancers have more mutations than others, but they all have mutations and that means that in every patient with a cancer . . . you could sequence their tumor DNA and make a vaccine for them.”

Linette said that microsatellite instability–high cancers such as colon, endometrial or other primary site tumors would be obvious candidates because of their high tumor mutational burden. “I think these are probably the proof of concept, proof of principle malignancies where these vaccines will be tested.”

He said it was difficult to say how long it would be before mRNA vaccines make a wide-ranging impact on cancer. However, he said the results of the mRNA-4157/V940-Keytruda trial would “certainly stimulate more clinical trials in this area.”

Moderna did not respond to BioSpace’s request for comment.

Heather McKenzie is a senior editor at BioSpace, focusing on neuroscience, oncology and gene therapy. You can reach her at heather.mckenzie@biospace.com. Follow her on LinkedIn: https://www.linkedin.com/in/heathermmckenzie/ and Twitter: @chicat08