When used alongside Merck’s Keytruda, Moderna’s personalized cancer vaccine halved the risk of death or disease recurrence in a mid-stage trial of advanced melanoma—a result analysts said could help “instill confidence” in the regimen.
An investigational regimen of Moderna’s personalized cancer vaccine and Merck’s mega-blockbuster PD-1 inhibitor Keytruda significantly improved survival in patients with stage 3 or 4 high-risk melanoma.
These findings, presented Monday at the annual meeting of the American Society of Clinical Oncology (ASCO) in Chicago, represent 5-year follow-up data from the Phase 2b KEYNOTE-942 trial. The ongoing study enrolled 157 participants who were assigned to receive Moderna’s mRNA-based shot intismeran autogene plus Keytruda or Keytruda alone. Results showed that after more than 60 months, the combo regimen slashed the risk of recurrence or death by 49% versus PD-1 treatment alone.
Intismeran autogene plus Keytruda likewise reduced the risk of distant metastasis or death by 59% and, in an exploratory analysis, boosted overall survival by 53%. Jefferies called these survival figures “encouraging” in a note on Monday morning, adding that the readout “helps instill confidence in pivotal Phase III data in 2026.”
Aside from survival outcomes, Moderna at ASCO also touted an overall acceptable safety profile for intismeran autogene. While immune-related toxicities arose in more than 45% of patients on the combo regimen, no grade 4 or 5 adverse events were reported. The most common side effects included fatigue, injection-site pain and chills, most of which were grade 1 or 2 in severity.
Moderna in recent months has been hit hard by the increasing skepticism toward mRNA technology, stoked by no less than health secretary Robert F. Kennedy, Jr., who in August last year axed more than 20 government-funded mRNA vaccine contracts, including some that had been granted to Moderna. The biotech has been coping by being prudent about which assets to invest in, leading to the discontinuation of three vaccine candidates in November 2025.
But in collaboration with Merck, Moderna is going all-in on its mRNA approach to cancer and has launched a sweeping development program for intismeran autogene and Keytruda, consisting of nine ongoing Phase 2 and Phase 3 studies across multiple cancers. One of these is the Phase 3 INTerpath-001 trial in adjuvant melanoma, which is expected to release interim data next year, according to Jefferies.
Monday’s Phase 2b findings “could have favorable readacross” to INTerpath-001, which is similarly looking at recurrence-free survival (RFS) as a primary endpoint, the analysts said. The group specifically stated that a hazard ratio of 0.5–0.8 on RFS—indicative of a 20% to 50% reduction in the risk of recurrence or death—“should be clinically meaningful.”
The firm expects Moderna’s vaccine to enter the market in 2027, but given its current 50-50 profit-sharing agreement with Merck, the vaccine “may result in a more meaningful sales contribution in 2028.” In adjuvant melanoma alone, intismeran autogene could open a “multi-billion dollar peak sales” opportunity for Moderna, analysts added.
