Experimental mRNA Vaccine Plus Keytruda Delays Melanoma Recurrence

A new study shows that a personalized messenger RNA (mRNA) cancer vaccine plus the checkpoint inhibitor Keytruda (pembrolizumab) reduced the risk of recurrence or death in people with high-risk advanced melanoma. The vaccine, mRNA-4157 (V940, being jointly developed by Moderna and Merck), uses the same mRNA technology as the Moderna and Pfizer-BioNTech COVID-19 vaccines.

With promising early results, a version of the vaccine called mRNA4157 (V940) was evaluated in the Phase IIb KEYNOTE-942 trial as a treatment for advanced melanoma. The study included 157 participants with stage III or IV cutaneous melanoma that had been completely removed within the prior 13 weeks, but it had spread to a lymph node, so they were considered at high risk for recurrence. They were randomly assigned to receive Keytruda for up to a year either alone (50 patients) or with the vaccine administered every three weeks for up to nine doses (107 patients).

Over two years of follow-up, the vaccine combination demonstrated “statistically significant and clinically meaningful improvement” over Keytruda alone. Recurrence-free survival rates at one year were 83.4 percent in the vaccine group versus 77.1 percent in the Keytruda monotherapy group. At 18 months, the corresponding rates were 78.6 percent versus 62.2 percent — a 44 percent reduction in the risk of recurrence or death.

Treatment was generally safe, but adverse events were common. Side effects were consistent with those observed in previous studies of Keytruda, and adding the vaccine did not substantially increase severe adverse events (25 percent in the vaccine group versus 18 percent in the Keytruda monotherapy group). Just over half of vaccine recipients reported mild or moderate injection site pain. “The novel mechanism of action of mRNA-4157 may both deepen the activity of pembrolizumab and broaden the population of patients that can benefit from immune therapy,” Ryan Sullivan, MD, of Mass General Cancer Center, and colleagues concluded.