Moderna and Merck & Co. are pushing ahead with the industry’s most-advanced experimental cancer vaccine, announcing Wednesday they’ve begun enrolling patients in a Phase 3 trial aimed at preventing the return of melanoma after surgery.
Initiation of the trial marks another milestone for a new type of cancer vaccine, one that’s personalized to the tumor mutations of each patient. The companies’ messenger RNA vaccine, which was invented by Moderna, can trigger an immune response to up to 34 “neoantigens,” or unique protein flags on the surface of tumors.
The partners are followed closely by Moderna’s mRNA rival BioNTech and its partner Roche, which are testing a combination of a cancer vaccine and the immunotherapy Keytruda in previously untreated melanoma patients, along with Gritstone Bio, which has an off-the-shelf vaccine.
Moderna and Merck’s trial will combine the vaccine, called V940 or MRNA-4157, with Keytruda, and compare the pairing to Keytruda alone. The study will involve people who have had their tumors surgically removed and are at high risk of their disease returning.
Researchers will measure recurrence-free survival as well as assess overall survival and the occurrence of “distant” spread, which can result in more severe disease. They plan on enrolling 1,089 patients, two-thirds of whom will receive the combination, and treating them for about one year.
To succeed, the combo will need to outperform Keytruda alone, which reduced the risk of death or recurrence by 35% in Stage II disease and 63% in Stage III disease, when compared to a placebo. In a previous Phase 2 trial, the vaccine combo reduced the risk of death or recurrence by 44% versus Keytruda alone.
A positive Phase 3 result will signal whether V940 can be approved, and whether it could be used in other types of cancer, William Blair analyst Myles Minter wrote in a recent investor note.
“If the Phase 2 results can be maintained in a Phase 3 trial, the individualized neoantigen therapy could be a pipeline-in-a-drug pairing with Keytruda in any of its currently approved oncology indications,” wrote Minter.
He cautioned that the six weeks needed to manufacture each individualized vaccine may limit its use in more severe disease, however.