What the trial found
A personalized mRNA vaccine for melanoma reduced the risk of cancer recurrence and death by 42% compared with standard treatment in a late-stage clinical trial, according to NBC News. The experimental vaccine, called intismeran, was developed by Moderna and Merck. Results are due to be presented Saturday at the European Society for Medical Oncology's annual meeting in Madrid.
The study enrolled 1,137 people with Stage 3 melanoma. All had undergone surgery to remove their tumors and were being treated with Merck's immunotherapy drug Keytruda. Of those, 757 also received the vaccine and 380 received a placebo.
After two years, 82% of patients who got the vaccine plus Keytruda had not had a recurrence. In the Keytruda-plus-placebo group, the figure was 70%.
How the vaccine works
Each dose is built for the individual patient. According to Dr. Georgina Long of the Melanoma Institute Australia, who led the trial, the excised tumor is sequenced to identify a distinctive fingerprint of abnormal proteins known as neoantigens. The vaccine trains the immune system to recognize and target them, much as a standard vaccine teaches the body to recognize a virus or bacteria.
Long said scans may suggest surgery removed all of the melanoma while invisible cancer cells remain. "This treatment is about mopping up the cancer cells we can't see," she said. Keytruda mobilizes immune cells called T cells to find and destroy cancer, and the vaccine also helps the immune system fight the disease.
Dr. Shirin Bajaj of Mount Sinai, who was not involved in the trial, said the vaccine is likely enhancing Keytruda's effect by mobilizing additional killer T cells. "It essentially creates an army of killer T cells that are meant to recognize the tumor," she said.
Speed, safety and cautions
The vaccine uses messenger RNA, the platform behind the Covid vaccines. Because every dose must be made for one patient, timing was a concern. Patients received theirs in a little over nine weeks on average. Dr. Robert Vonderheide of Penn Medicine's Abramson Cancer Center, who was not involved, said the question was whether it could be done in a few weeks, and "the answer to that is yes."
Side effects included pain at the injection site and a mild fever, similar to those seen with Covid vaccines. Dr. Gino In of the USC Keck School of Medicine, also not involved, said that is a major selling point. Other drugs tested alongside this class of immunotherapies in earlier trials led to significant side effects, including immune attacks on the body's own tissue, he wrote in an email.
Investors reacted poorly when the findings leaked Thursday, and Moderna's stock fell. Bajaj suggested one reason may be that the added benefit over Keytruda alone is still relatively modest. She said it is hard to know whether the data show "the next blockbuster." The full data have not yet appeared in a peer-reviewed journal, and patients must be followed for several more years to see whether the benefit lasts and whether survival improves.
Bajaj also raised scalability. Of 1,749 melanoma patients initially screened, 17% did not have tumor samples large enough to make a vaccine. She said nothing in the study made her think the logistics were infeasible, but that scaling up would be a hurdle.
What comes next
Vonderheide called the results a "game changer" and a welcome lift for a field that has seen setbacks. In recent months, BioNTech announced trial failures for experimental vaccines against colorectal and head and neck cancers. He suggested intismeran may have succeeded because the trial targeted recurrence rather than prolonging survival in patients with more advanced disease. "Vaccines work to prevent," he said.
Intismeran is being studied in a separate trial in advanced melanoma that has spread to distant organs. Long called the current result "just the proof of concept" and said work is under way in bladder, kidney and lung cancers. Researchers will also try to learn why the vaccine worked.
Vonderheide said that using a vaccine to prevent cancer in the first place is a "very ambitious, far-off goal," but one these results bring closer.
