Moderna’s Personalized mRNA Vaccine Halves Melanoma Recurrence Risk

An experimental personalized mRNA vaccine developed by Moderna shows significant promise in reducing the risk of melanoma returning, according to new clinical trial results presented at the American Society of Clinical Oncology’s annual meeting and published in the Journal of Clinical Oncology. Melanoma, the deadliest form of skin cancer, often recurs within five years after treatment, particularly in patients with Stage 3 disease or higher.

The trial involved 157 patients in the United States and Australia who had undergone surgery to remove their tumors. All participants received standard immunotherapy with pembrolizumab (Keytruda), while 107 patients also received the personalized vaccine tailored to their tumor’s unique genetic mutations. After five years, nearly 69% of patients in the vaccine group remained cancer-free, compared to 49% in the group receiving only immunotherapy. The vaccine also reduced the risk of metastasis by nearly 60% and improved five-year survival rates, with 92% of vaccinated patients alive versus 71% in the control group.

Dr. Janice Mehnert, senior investigator and director of the melanoma program at NYU Langone Health, explained that the vaccine trains the immune system to recognize and attack cancer cells by targeting neoantigens—unique proteins formed by tumor-specific DNA mutations. Each vaccine encodes information for up to 34 neoantigens, enabling T cells to identify and destroy residual cancer cells that remain after surgery and immunotherapy.

“This is an incredibly interesting trial because the approach is just so unique,” Mehnert said. “It is a personalized immunotherapy strategy tailored to each patient’s tumor.”

The vaccine doses were administered up to nine times, beginning about four to six weeks after surgery and coordinated with pembrolizumab treatments. Side effects were generally mild and similar to those seen with mRNA COVID-19 vaccines, including flu-like symptoms such as chills and headaches lasting a few days.

Experts not involved in the study highlighted the potential impact of these findings. Dr. Sarah Arron, a dermatologist and skin cancer surgeon, called the results “a landmark advance” in treating high-risk melanoma, emphasizing the difference between this personalized mRNA vaccine and the uniform COVID-19 vaccines. “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 said.

Dr. Shailender Bhatia of Fred Hutchinson Cancer Center noted the vaccine’s low toxicity compared to other combination therapies, which often increase side effects without added benefit. “If this is successful, this will open up a new field relevant not just to melanoma, but many other cancers,” he said.

The vaccine, called intismeran, was developed by Moderna in collaboration with Merck, the maker of Keytruda. A larger Phase 3 trial involving nearly 1,000 patients across the U.S. and Europe is underway, with results expected soon. If confirmed, these findings could lead to FDA approval and a paradigm shift in melanoma treatment.

For patients like Connie Franciosi, who participated in the trial after a late-stage melanoma diagnosis in 2020, the vaccine has been life-changing. “I am cancer-free,” she said. “Life is good.” Now 80 years old, Franciosi enjoys gardening, playing golf, and spending time with friends.

Researchers are also exploring the use of mRNA vaccines to prevent recurrence in other cancers, including pancreatic and lung cancers, building on the advances in mRNA technology accelerated by the COVID-19 pandemic.