The excitement was not simply about a potential new treatment for melanoma. The trial offers some of the strongest evidence yet that mRNA technology – best known for its role in COVID-19 vaccines – could also have an important future in cancer treatment.
Reuters reported that intismeran, when combined with Merck’s immunotherapy drug Keytruda, met the primary endpoints of the large Phase 3 trial.
If the same approach proves successful against other tumors, personalized mRNA vaccines could eventually become a new weapon against a range of cancers.
How the Vaccine Works
Despite the name, intismeran is not a vaccine in the familiar sense. It is not given to healthy people to stop them from developing cancer, as a flu vaccine might prevent influenza or a measles vaccine might prevent measles.
It is a treatment for people who have already had cancer, designed to teach their immune system to recognize and destroy cancer cells that may still be lurking in the body.
The INTerpath-001 trial enrolled patients with stage IIB to IV melanoma whose tumors had been completely removed by surgery. Even after successful surgery, however, microscopic cancer cells can remain undetected and later cause the disease to return. Intismeran is designed to help the immune system hunt down those remaining cells.
The trial involved 1,137 patients. Two-thirds received intismeran together with Keytruda, while the remaining third received Keytruda alone.
Made to Measure
What makes intismeran unusual is that there is no single version of the vaccine. Each patient receives one made specifically for them.
Scientists begin with a sample of the patient’s tumor and analyze its mutations, searching for features that distinguish the cancer cells from healthy cells. From these, they identify targets known as neoantigens – effectively creating a genetic fingerprint of that patient’s cancer.
A personalized mRNA treatment is then produced containing instructions for up to 34 of these neoantigens. The aim is to train T cells, a key part of the immune system, to recognize and attack cancer cells carrying those markers. Moderna has described the process in detail.
In simple terms, doctors are showing the immune system a molecular picture of the enemy they want it to attack. CBS News compared it to giving a tracking dog the scent of what it is supposed to find.
A Two-Pronged Attack
Patients received intismeran alongside Keytruda, or pembrolizumab, an established immunotherapy drug known as a checkpoint inhibitor.
Tumors can exploit mechanisms that normally prevent the immune system from attacking healthy tissue, effectively using the body’s own brakes to protect themselves. Keytruda blocks one of those mechanisms by targeting a receptor called PD-1, making it easier for the immune system to attack the cancer.
The two treatments are therefore intended to work together. Intismeran helps the immune system identify its target, and Keytruda makes it easier to attack it.
That distinction matters. The trial does not show that Moderna’s vaccine beat cancer. It shows that patients did better when the personalized vaccine was added to Keytruda than when they received Keytruda alone.
What the Trial Found
The trial achieved both of its main goals.
The first was recurrence-free survival – how long patients remained alive without their cancer returning. Patients who received intismeran and Keytruda did better on this measure than those who received Keytruda alone.
The second was distant metastasis-free survival, which measures how long patients remain alive without the cancer spreading to other parts of the body. The combination also performed better on this measure.
Moderna and Merck say the improvements were both statistically significant and clinically meaningful. According to the companies, this is the first personalized neoantigen therapy, as well as the first mRNA cancer therapy, to deliver positive results in a Phase 3 trial.
The findings follow promising results from an earlier Phase 2b study. With longer follow-up, intismeran plus Keytruda reduced the risk of recurrence or death by approximately 49% and the risk of distant metastasis or death by 59% compared with Keytruda alone.
The Missing Numbers
There is an important caveat. Moderna and Merck have announced that the Phase 3 trial succeeded, but they have not yet published the full results.
That means we know the combination performed significantly better than Keytruda alone, but we do not yet know the size of that advantage. The companies plan to present the detailed results at an international medical conference.
Nor do we know yet whether intismeran helps patients live longer.
Overall survival is a secondary endpoint of the trial, but the data are not yet mature enough to answer that question. For now, the evidence shows that intismeran delayed the return or spread of cancer, but not yet that it prolonged patients’ lives.
Beyond Melanoma
That is the question that could ultimately make these results much more significant.
Moderna and Merck are already testing intismeran more widely. Their INTerpath research program includes nine Phase 2 and Phase 3 trials, with the technology being studied in other cancers including non-small cell lung cancer, bladder cancer and kidney cancer.
The approach is potentially adaptable because it is not built around a biological feature unique to melanoma. The treatment is designed around mutations found in each individual tumor.
In principle, the same process could therefore be used against very different cancers – provided clinical trials show that it works.
That is the real significance of the melanoma result. Moderna has not developed a universal vaccine against cancer. But a personalized mRNA cancer therapy has now succeeded in a pivotal Phase 3 trial for the first time.
A New Era of Cancer Treatment
The development fits into a much broader change in the way cancer is treated.
As The Economist noted in an analysis last year, progress against cancer is not being driven by a single miracle cure. It is coming from earlier diagnosis and prevention, alongside treatments increasingly tailored to the biology of individual tumors.
Chemotherapy indiscriminately attacks rapidly dividing cells. Targeted drugs exploit particular weaknesses in cancer cells. Immunotherapy helps the immune system recognize and attack them.
Personalized vaccines push that logic further. Instead of simply developing a drug for a particular type of cancer, scientists can potentially design a treatment around the mutations found in one patient’s tumor.
If the technology succeeds in other cancers, the future "cancer vaccine" may therefore look nothing like the universal injection the phrase suggests.
There may never be one single vaccine for cancer. Instead, there could be thousands of them – individually designed to teach each patient’s immune system how to recognize their own disease.
That future is still some way off. Intismeran has not yet been approved, the full Phase 3 results have not been released and there is not yet evidence that it extends overall survival.
But the trial represents an important step. Cancer’s extraordinary genetic diversity has always made the disease difficult to treat. Personalized mRNA technology raises an intriguing possibility: that the same diversity could one day be used to tell the immune system exactly what to attack.
