Moderna-Merck cancer vaccine success raises questions over its use against other cancers

A personalised cancer vaccine developed by pharmaceutical companies Moderna and Merck has achieved a significant milestone in a late-stage clinical trial, reducing the risk of melanoma returning or causing death when used alongside an existing immunotherapy drug. However, questions remain about how the treatment produces its benefits and whether similar results can be achieved against other forms of cancer.

The findings from the Phase 3 INTerpath-001 trial, involving 1,137 patients with high-risk melanoma, showed that adding the experimental vaccine intismeran autogene to Merck's immunotherapy drug Keytruda reduced the risk of cancer recurrence or death by 42%, compared with Keytruda alone.

Detailed results were presented at the European Society for Medical Oncology (ESMO) Congress 2026. The findings mark an important development in personalised cancer treatment, but researchers caution that the success in melanoma does not establish that the same approach will work across different cancers.

How the personalised cancer vaccine works

Unlike conventional vaccines designed to prevent infectious diseases, intismeran autogene is intended to help the immune system recognise and attack cancer cells.

The treatment uses messenger RNA (mRNA) technology to produce proteins corresponding to mutations found in an individual patient's tumour. These mutations, known as neoantigens, can help the immune system distinguish cancer cells from healthy cells.

To develop the vaccine, researchers analyse a patient's tumour and identify genetic mutations that could serve as targets. The resulting personalised vaccine carries instructions for the immune system to recognise these targets and mount a response against cells carrying them.

The vaccine is administered alongside Keytruda, an immunotherapy that helps the immune system attack cancer by blocking the PD-1 pathway, which cancer cells can exploit to evade immune responses.

In the INTerpath-001 trial, patients received the combination after surgery to remove stage IIB to IV melanoma. The study compared the outcomes of patients receiving intismeran autogene and Keytruda with those receiving Keytruda and a placebo.

Trial results show lower risk of melanoma recurrence

The trial enrolled 1,137 patients who had undergone complete surgical removal of their melanoma. After a median follow-up of 24.6 months, the combination treatment reduced the risk of recurrence or death by 42% compared with Keytruda alone.

At the two-year mark, 82.2% of patients receiving the vaccine combination remained free of cancer recurrence, compared with 70% of those receiving Keytruda alone.

The combination also reduced the risk of cancer spreading to distant parts of the body or death by 38%. The two-year distant metastasis-free survival rate was 88.5% among patients receiving the combination, compared with 80.2% in the Keytruda-only group.

However, the researchers have not yet established whether the treatment improves overall survival. The trial is continuing to monitor patients to assess longer-term outcomes.

The most commonly reported treatment-related adverse events in the combination group included fever, injection-site pain and fatigue. The companies reported no new safety signals in the trial.

Why researchers are cautious about wider applications

Despite the encouraging melanoma results, scientists are still trying to understand why the personalised vaccine works in some settings and whether it can be effective against other cancers.

One challenge is that cancers differ considerably in their genetic mutations and the way they interact with the immune system. Melanoma is generally considered more responsive to immunotherapy than certain other cancers, while some tumours create an environment that makes it difficult for immune cells to recognise and attack them.

The uncertainty has become more evident following setbacks in other cancer vaccine studies. BioNTech and its partner Genentech discontinued a Phase 2 trial of their experimental mRNA cancer vaccine for colorectal cancer after the treatment failed to demonstrate the expected benefit.

Researchers have cautioned against directly comparing the two studies, as they involved different cancer types and treatment approaches. The Moderna-Merck vaccine was administered with Keytruda, while the colorectal cancer vaccine was tested as a standalone treatment.

The differing outcomes have nevertheless raised questions about the role of tumour biology, immune response and combination therapies in determining whether personalised cancer vaccines succeed.

Research continues into other cancer types

Moderna and Merck are among several pharmaceutical companies exploring whether personalised mRNA technology can be used against cancers beyond melanoma.

Research is also underway into its potential applications in lung, pancreatic and other cancers. However, these studies remain at different stages of clinical development, and the melanoma findings cannot yet be treated as evidence of effectiveness against these diseases.

The Phase 3 results represent a significant step for personalised cancer vaccines, but further research and longer-term patient monitoring will be needed to establish their benefits, limitations and potential role in cancer treatment.

The vaccine remains investigational, and the companies are engaging with regulatory authorities on possible next steps towards approval.