NEW YORK — Moderna and Merck reported five-year results from a Phase 2 clinical trial showing their personalized mRNA melanoma vaccine, intismeran, combined with Keytruda reduced recurrence and improved survival in high-risk patients. The trial included 157 patients in Australia and the U.S. who had undergone surgery to remove Stage 3 or higher melanoma tumors.
After five years of follow-up, 68.8% of patients who received the combination therapy remained cancer-free, compared with 49.1% of those who received Keytruda alone, representing a 49% reduction in recurrence risk. Additionally, 92% of patients in the combination group were alive at five years, compared to 71% in the Keytruda-only group. The combination also cut the risk of cancer metastasizing by nearly 60%.
The vaccine, developed by Moderna and tested in collaboration with Merck, the maker of pembrolizumab (marketed as Keytruda), uses genetic material from each patient’s tumor to identify up to 34 neoantigens. Patients received up to nine vaccine doses spaced about three weeks apart alongside immunotherapy. Side effects were mild and similar to those seen with mRNA COVID-19 vaccines, including chills, headaches, and minor pain at the injection site.
"This is an incredibly interesting trial because the approach is just so unique," said Dr. Janice Mehnert, a melanoma specialist and researcher at NYU Langone Health and senior author of the paper analyzing the trial results. "It is a personalized immunotherapy strategy," tailored to each patient's tumor. "We're trying to harness the power of the immune system early in a patient's disease course to optimize their outcomes," she said. "That's pretty exciting." Mehnert also noted, "I think this is strong evidence that this therapy, when used in combination with immunotherapy, can demonstrably reduce the risk of dying from this disease."
Dr. Sarah Arron, a dermatologist and skin cancer surgeon in the San Francisco Bay Area who was not involved in the research, said, "I think this is a landmark advance in how we treat these very advanced, high-risk melanomas." She added, "The COVID vaccine was the same RNA fragment given to everybody. Whereas in this case, the antigen itself is not one virus, it's [each] patient's tumor." Arron also said, "By matching this RNA treatment to the patient's melanoma, we can really boost the immunotherapy by driving it toward the patient's tumor." She noted, "This mRNA vaccine is designed towards boosting a tumor response."
Moderna chief development officer Dr. David Berman said, "The results are exciting." A Phase 3 trial with nearly 1,000 patients is now underway, with the goal of seeking FDA approval after results are analyzed. The study was funded by Moderna and a Merck subsidiary and was presented at the American Society of Clinical Oncology conference and published in the Journal of Clinical Oncology.