For people with high-risk melanoma removed by surgery, a personalized mRNA treatment added to Keytruda lowered the risk of recurrence or death in a large Phase 3 trial.
What the trial found
The international INTerpath-001 trial enrolled 1,137 people with completely removed stage IIB–IV melanoma who had not received prior systemic treatment. Half received Keytruda (pembrolizumab) plus the investigational vaccine intismeran autogene; the comparison group received Keytruda alone. After a median follow-up of 24.6 months, the combination lowered the hazard, or rate over time, of recurrence or death by 42%, and of distant spread or death by 38%. The results were presented at the European Society for Medical Oncology congress on October 24.
The 42% figure is a relative reduction, not a 42-percentage-point increase in the number of people who avoid recurrence, and it does not mean the treatment cures 42% of patients. At two years, an estimated 82.2% of people on the combination were alive without recurrence, compared with 70.0% on Keytruda alone, a difference of 12.2 percentage points. Overall survival is not yet established: those data are still immature, and the study is continuing.
Why add a vaccine after surgery
Surgery can remove visible melanoma, but microscopic cancer cells may remain and later cause recurrence or spread. Keytruda is already used after surgery to lower that risk. The FDA approved it for resected stage III melanoma in 2019 and stage IIB or IIC in 2021, but some patients still relapse.
An earlier randomized Phase 2b study, KEYNOTE-942, tested the same combination in 157 people with resected stage IIIB–IV melanoma. It reported better recurrence-free survival than Keytruda alone, and five-year follow-up continued to show a benefit. That result led the companies to test the approach in a larger Phase 3 trial covering a broader range of stages. The new finding supports the earlier result, but does not settle every question.
How the personalized treatment works
Intismeran is not a vaccine to prevent melanoma in healthy people. It is made for someone who has already had cancer, using a sample of their tumor to identify mutations that may distinguish cancer cells from healthy cells. The companies say the mRNA can encode up to 34 tumor-specific targets, called neoantigens. After injection, cells use the instructions to produce the targets and show them to the immune system, training T cells to recognize them. The mRNA is temporary and does not become part of a person’s DNA.
Keytruda works differently: it blocks PD-1, a protein that can act as a brake on T cells. The idea is that the vaccine directs immune cells toward the tumor’s distinct targets while Keytruda helps keep the immune response active. This is a possible explanation for the combination, not proof that the drugs work the same way in every cancer.
What patients still need to know
In a pre-specified analysis, recurrence outcomes were similar in both groups during the first six months; the advantage became clearer later. That may fit the time needed to build an immune response, but it also means any benefit may not be immediate. The companies reported no new safety signals, though patients and clinicians will weigh the added injections and treatment against the possible reduction in recurrence.
Because each dose is tailored to one person, the treatment is not an off-the-shelf product. Merck’s CEO told CNBC that the current process takes about six weeks from tumor sequencing to delivery to the hospital. Manufacturing speed, supply and insurance coverage will affect access. The trial does not answer those questions, and the companies have not announced a price.
Next steps for the vaccine
Intismeran remains investigational. Merck and Moderna say they are engaging with regulators, while the trial continues to measure overall survival. Moderna’s CEO told CNBC the company is preparing a U.S. filing and aims for a 2027 launch; that is a company target, not an approval decision. Regulatory review and longer follow-up will help show whether the vaccine delays recurrence, helps patients live longer and can be delivered widely.