About 12 More in 100 Melanoma Patients Stay Cancer-Free With a Custom Vaccine

A personalised cancer vaccine improved recurrence-free outcomes after melanoma surgery in a large phase 3 trial, bringing treatment designed around each patient's tumour closer to clinical use. ^[2]

At 24 months, 82.2% of patients given Moderna and Merck's vaccine alongside pembrolizumab were alive without their cancer returning, compared with 70.0% given pembrolizumab alone. That is a difference of 12.2 percentage points, or roughly 12 more people in every 100 alive and recurrence-free at that point. ^[2]

The vaccine, intismeran autogene, targets mutations in an individual patient's cancer. The trial tested it after surgeons had removed the visible tumour, when people with high-risk melanoma still face the possibility that cancer will return or spread. Pembrolizumab, an immunotherapy already used in this setting, was given to both groups. ^[1][2]

Independent researchers expect the findings could lead to approval next year. Alan Melcher, a cancer researcher quoted by New Scientist, said approval could come quickly and that next year sounded reasonable. Rebecca Lee, who was not involved in the trial, said approval in the US, Europe and the UK next year was highly likely. ^[1]

Those are expert expectations, not regulatory decisions. The companies say they are engaging with regulators, but no firm approval timetable has been established. Nor do the results yet show that patients live longer overall, because the survival data need more follow-up. ^[2]

A substantial gain after surgery

The INTerpath-001 trial enrolled 1,137 adults whose high-risk stage IIB to IV cutaneous melanoma, the form arising in the skin, had been surgically removed. Researchers randomly assigned 757 to the vaccine combination and 380 to pembrolizumab with a placebo. The study was double-blind, meaning neither patients nor the staff assessing them knew who received the vaccine. ^[2]

This design gives the result weight. Random assignment makes the groups more comparable, while a placebo and blinding reduce the chance that expectations about a new treatment distort the comparison.

After a median follow-up of 24.6 months, the trial's analysis found a 42% lower risk of recurrence or death in the combination group. It also found a 38% lower risk of cancer spreading to distant parts of the body or death. ^[2]

The 42% figure describes the relative reduction in risk across the follow-up period. It is a different measure from the 12.2-percentage-point gap between the groups at 24 months. Both measure an improvement, but the latter gives patients a more concrete picture of the difference at a particular point in time. ^[2]

Recurrence-free survival counts either a return of cancer or death as an event. For someone who has undergone surgery, avoiding a recurrence is a valuable outcome in itself. The purpose of this treatment is to improve the odds during a period when the visible cancer is gone but the danger has not passed. ^[2]

A vaccine with an individual target

Making the vaccine starts with a sample of the patient's tumour. Researchers sequence its DNA and compare it with DNA from healthy blood cells, looking for mutations specific to the cancer. They then make an mRNA vaccine encoding up to 34 of those targets. ^[1][2]

The aim is to teach immune cells called T cells to recognise that patient's tumour. Pembrolizumab complements the vaccine by helping prevent those T cells from becoming exhausted, allowing them to keep attacking cancer. The two treatments therefore address different parts of the same task: recognising the target and sustaining the response. ^[1]

This is a treatment vaccine for people who have already had cancer, rather than an injection to prevent melanoma in healthy people. Its defining feature is that the instructions change with the patient's tumour. ^[1][2]

The trial regimen was substantial. Patients received pembrolizumab every six weeks for up to nine cycles, alongside vaccine or placebo injections every three weeks for up to nine doses. ^[2]

Side effects also matter in patients whose tumours have already been removed. Grade three or higher adverse events, meaning medical problems rated severe or worse on a standard scale, occurred in 23.6% of the combination group and 20.3% of the control group, regardless of their attributed cause. Fever, injection-site pain and fatigue were among the frequent adverse events with the combination. ^[2]

The safety figures put a cost alongside the benefit: adding the vaccine improved recurrence-free outcomes, while the proportion experiencing higher-grade adverse events rose by 3.3 percentage points. Treatment decisions will have to account for both. ^[2]

Approval would open the access question

The potential patient population is sizeable. New Scientist reports about 19,400 melanoma diagnoses annually in the UK, with roughly one-quarter considered high risk. Lee said thousands of people in the UK alone could benefit, based on the trial population. ^[1]

Individual manufacture could make access expensive. New Scientist cited a January Reuters estimate of about $200,000 per treatment, but that is not a confirmed launch price. Moderna and Merck did not answer its question about pricing. ^[1]

Even with regulatory approval, health systems would need to decide whether and how to pay for a treatment manufactured separately for each patient. A successful trial establishes medical value. It does not settle who can obtain it.

Melcher said further research should identify which patients benefit most, including whether markers in blood or the tumour could predict response. That could help doctors make more selective treatment decisions. ^[1]

The companies released the phase 3 findings on October 22, ahead of a planned presentation at a presidential symposium of the European Society for Medical Oncology congress. The findings have been accepted for publication in The New England Journal of Medicine, according to Targeted Oncology. Follow-up continues, with the congress presentation set to provide the next detailed examination of the results. ^[2][3]