For a patient who has just had a melanoma cut out, the scan may look clean. The fear is what the scan cannot see. A personalized mRNA vaccine from Moderna and Merck has now cut the risk of melanoma recurrence or death by 42% compared with standard treatment in a late-stage trial, and some oncologists are calling it a major breakthrough.
Behind the breakthrough
The vaccine, called intismeran, is built from each patient’s own tumor. Dr. Georgina Long, co-medical director of the Melanoma Institute Australia, who led the trial, said the excised tumor is sequenced and a fingerprint of abnormal proteins, known as neoantigens, is identified. The vaccine trains the immune system to find and attack them, much as a standard vaccine does with a virus. “This treatment is about mopping up the cancer cells we can’t see,” Long said.
It works alongside Merck’s Keytruda, which mobilizes T cells to spot and destroy cancer. Dr. Shirin Bajaj of Mount Sinai, who was not part of the trial, said the vaccine likely adds to that by raising “an army of killer T cells” aimed at the tumor.
The messenger RNA platform is the same one pioneered with Covid vaccines, and speed was the question. “They’re not on the shelf,” said Dr. Robert Vonderheide, director of Penn Medicine’s Abramson Cancer Center. Each dose has to be made for one person. Patients received theirs in a little over nine weeks on average, and Vonderheide said that proved a timely turnaround is possible.
The numbers
The trial enrolled 1,137 patients with Stage 3 melanoma, meaning the cancer had reached nearby lymph nodes or other skin sites but not distant organs. All had surgery and were treated with Keytruda. Of those, 757 also received the vaccine and 380 a placebo. Two years on, 82% of the vaccine group had no recurrence, against 70% on Keytruda and placebo. Recurrence is the “dreaded event” for these patients, Vonderheide said, because spread to distant organs becomes more likely.
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 called that a major selling point, since other drugs combined with Keytruda-type immunotherapies have produced worse and sometimes permanent side effects.
What is still unknown
The full data has yet to appear in a peer-reviewed journal, and patients need following for several more years to see whether the benefit lasts and whether survival improves. Bajaj noted that the gain over Keytruda alone is still relatively modest. She also pointed to logistics: of 1,749 melanoma patients screened for the trial, 17% lacked a tumor sample big enough to make a vaccine. Nothing in the study made her think the logistics are infeasible, she said, only that scaling up will be a hurdle.
Vonderheide said the result is a welcome lift for a field that has seen disappointments, including recent BioNTech failures in colorectal and head and neck cancers. He suggested success here may owe to targeting recurrence rather than late-stage disease. Intismeran is also being tested in advanced melanoma that has spread to distant organs, and Long said work is under way in bladder, kidney and lung cancers. Patients should talk to their oncologist about what any of this means for them.
Wall Street was not impressed
Investors read the numbers differently. According to 24/7 Wall St., Moderna stock fell 4% to $193.62 in morning trading, after an 18% plunge the session before, as the full data landed short of the hopes built during a rally that began in August. Merck slipped 0.8% to $146 and Pfizer 0.7% to $30.22, while the iShares Biotechnology ETF held at $209.54. The difference is exposure. Every approved Moderna product is a respiratory vaccine, among them Spikevax, Mnexspike, Mresvia and Mflusiva, so oncology carries much of its long-term promise. For Merck, the vaccine is an add-on to Keytruda.
Sources
- Moderna
- Moderna Sinks 4% After 18% Plunge as Melanoma Vaccine Selloff Extends; Merck and Pfizer Slip
- Personalized mRNA vaccine for melanoma cut risk of cancer’s return in late-stage trial
Photo: Xuthoria (CC BY-SA 4.0)
