Personalized mRNA treatment reduces melanoma recurrence in landmark Phase 3 trial

Inova Schar Cancer was among the trial’s leading-enrolling sites, with participation led by principal investigator Dr. Sekwon Jang.

A personalized mRNA-based treatment reduced the risk of melanoma returning or causing death by 42% when added to the immunotherapy Keytruda, according to Phase 3 results presented at the 2026 European Society for Medical Oncology Congress. 

The findings mark the first successful Phase 3 trial of a cancer treatment customized to the mutations in an individual patient’s tumor. It is also the first mRNA-based cancer treatment to reach this milestone. 

“This has the potential to be a major breakthrough in melanoma treatment,” Dr. Sekwon Jang told CNBC. 

Dr. Jang is Siewick Director, Cancer Research; Director, Melanoma Research and Therapeutics; and Co-Director, Melanoma and Skin Cancer Center at Inova Schar Cancer. He served as Inova’s principal investigator and led the study at Inova for the INTerpath-001 trial. 

Inova was among the study’s leading-enrolling sites and the only participating site in Virginia and the Washington, DC, region. 

What the Phase 3 study found 

INTerpath-001 included 1,137 patients whose high-risk melanoma had been completely removed through surgery. Patients received either Keytruda alone or Keytruda with intismeran autogene, an investigational treatment created specifically for each patient. 

Researchers followed patients for about two years. The results showed: 

• Adding intismeran to Keytruda reduced the risk of melanoma recurrence or death by 42% 

• The combination reduced the risk of melanoma spreading to other parts of the body or causing death by 38% 

• At two years, 82.2% of patients receiving the combination remained cancer-free, compared with 70% receiving Keytruda alone 

• No new safety concerns were identified 

The study is continuing to evaluate overall survival, so researchers cannot yet say whether the combination helps patients live longer. 

“With this combination, I think the risk-benefit ratio actually is much more favorable,” Dr. Jang told Bloomberg. 

How is the treatment personalized? 

Intismeran is not an off-the-shelf vaccine. After a patient’s melanoma is removed, the tumor is analyzed to find changes that are unique to that person’s cancer. Scientists then identify which changes are most likely to help the immune system recognize the cancer and use that information to create a personalized mRNA treatment. 

The treatment teaches the immune system what to look for so it can recognize and attack cancer cells with those changes. Keytruda helps by releasing the “brakes” that can stop the immune system from attacking cancer. 

Unlike vaccines that prevent infections, this is a therapeutic cancer vaccine designed to help prevent melanoma from returning after surgery. 

What comes next? 

Intismeran remains investigational and is not yet approved by the U.S. Food and Drug Administration (FDA). Merck and Moderna plan to submit the Phase 3 findings to the FDA and other health authorities. 

Researchers are also studying this personalized approach in other cancers including lung, kidney and bladder cancers. Inova is participating in additional research evaluating intismeran with Keytruda for advanced melanoma that cannot be removed through surgery. 

The findings point to a future in which cancer treatment could be tailored not only to the type of cancer, but also to the unique features of each patient’s tumor.