Cancer therapy breakthrough: Vaccine cuts skin cancer recurrence risk in landmark trial

Previous studies had suggested that personalised cancer vaccines might work. The new trial result provides the strongest evidence so far that adding such a vaccine to an established immunotherapy can deliver additional clinical benefit. It is also being described as the first successful late-stage trial of an mRNA-based personalised cancer vaccine. However, this is not intended to prevent cancer from developing in the first place but prevent recurrence with other therapies.

What is the vaccine about?

The treatment, known as intismeran autogene, is not a conventional vaccine manufactured in bulk and given identically to millions of people. It is personalised.

After a melanoma tumour is surgically removed, doctors analyse its genetic material. Researchers look for mutations that are present in the cancer but absent from normal cells. Many tumours contain abnormal proteins that can potentially serve as distinctive markers for the immune system. This information is then used to design an individualised mRNA treatment containing instructions linked to those tumour-specific targets. The objective is to show the immune system what the patient’s cancer looks like, then encourage it to remember the imprint and attack those cells.

How mRNA vaccine works in skin cancer

The vaccine-drug combo

The Moderna-Merck strategy combines the personalised vaccine with Keytruda (pembrolizumab), one of the world’s best-known cancer immunotherapies. The two treatments have different jobs.

The mRNA vaccine essentially provides the immune system with a list of targets. Keytruda helps remove an immune “brake” that cancers can exploit to avoid destruction. Together, the idea is to create a more focussed and sustained immune assault against residual cancer cells that may remain after surgery.

So the vaccine is not intended simply to prevent someone from developing melanoma in the first place. It is being developed primarily as an adjuvant treatment, given after surgery to reduce the chances that an already treated cancer will return.

The breakthrough trial

The Phase 3 INTerpath-001 study enrolled 1,137 people with high-risk stage IIB to IV melanoma whose tumours had been surgically removed. Patients received either Keytruda alone or Keytruda together with the personalised mRNA treatment.

The combination met its two major efficacy goals. It reduced the risk of melanoma returning and also reduced the risk of the disease spreading to distant parts of the body. Earlier follow-up from a Phase 2 study had already provided encouraging evidence. Five-year results indicated that adding the personalised vaccine to Keytruda substantially reduced the risk of melanoma recurrence and distant spread compared with Keytruda alone. The latest trial has now strengthened that case.

Why it was tested on melanoma patients

Melanoma is an attractive target for personalised cancer vaccines because melanoma cells often carry a large number of genetic mutations. This means more abnormal proteins for the immune system to distinguish from healthy tissue and learn from.

Tumours differ enormously in their biology and in the extent to which the immune system can recognise them. But the principle could potentially be applied across a much wider range of cancers.

Beyond skin cancer

Moderna and Merck are already testing related approaches in non-small-cell lung cancer, while other studies are examining bladder, kidney, pancreatic and stomach cancers. Other pharmaceutical companies are pursuing similar personalised vaccine technologies. BioNTech and Roche, for example, are investigating an individualised mRNA treatment in colorectal and pancreatic cancers.

What about vaccine availability?

There is, however, a formidable practical obstacle. A conventional vaccine can be manufactured in enormous quantities because essentially every dose is the same. A personalised cancer vaccine is different as every cancer needs a different formulation. That means tumour sequencing, vaccine design and manufacturing must all happen quickly and reliably. Scaling such a system is, therefore, challenging.

Cost will also matter. A treatment that is successful but expensive or difficult to manufacture could struggle to become widely accessible.

As of now, this is a breakthrough, not a cure. The excitement surrounding the results should not obscure what remains unknown. Researchers still need longer follow-up to determine whether the treatment ultimately improves overall survival, not simply the time before recurrence or distant spread. Regulatory approval is required.