Moderna’s personalized cancer vaccine combined with Merck’s PD-1 inhibitor Keytruda significantly improved survival in patients with stage 3 or 4 high-risk melanoma, according to data presented on June 2 at the annual meeting of the American Society of Clinical Oncology in Chicago.
The findings are based on five-year follow-up results from the Phase 2b KEYNOTE-942 trial, which enrolled 157 participants. Patients received either Moderna’s mRNA-based shot intismeran autogene plus Keytruda or Keytruda alone. After more than 60 months, the combination regimen reduced the risk of recurrence or death by 49% compared to PD-1 treatment alone. The combination also lowered the risk of distant metastasis or death by 59%, and an exploratory analysis showed a boost in overall survival by 53%. Jefferies analysts called these figures “encouraging,” and said they “help instill confidence in pivotal Phase III data in 2026.”
In addition to efficacy outcomes, Moderna reported that intismeran autogene demonstrated an overall acceptable safety profile. More than 45% of patients receiving the combination experienced immune-related toxicities; however, no grade 4 or grade 5 adverse events were observed. The most common side effects included fatigue, injection-site pain, and chills—mostly classified as grade 1 or grade 2 severity.
Recently, Moderna has faced skepticism regarding mRNA technology following actions by health secretary Robert F. Kennedy, Jr., who canceled over twenty government-funded mRNA vaccine contracts last August—including some awarded to Moderna. In response, Moderna discontinued three vaccine candidates in November but continues its collaboration with Merck on intismeran autogene and Keytruda across nine ongoing Phase 2 and Phase 3 studies for multiple cancers.
One such study is INTerpath-001, a Phase III trial in adjuvant melanoma expected to release interim data next year. Monday’s findings could have "favorable readacross" to this trial since both focus on recurrence-free survival as a primary endpoint. Jefferies analysts noted that a hazard ratio between 0.5–0.8 for recurrence-free survival should be clinically meaningful.
Analysts expect Moderna’s vaccine could enter the market in 2027 under its current profit-sharing agreement with Merck, but anticipate more significant sales contributions starting in 2028 if approved.
