Personalised melanoma vaccine cuts death or recurrence risk by 42%

By Daniel Okafor

A personalised mRNA melanoma vaccine reduced the risk of death or recurrence by 42% when added to Keytruda in a phase 3 trial of 1,137 adults, according to the reported results.

The report described the trial as a world-first test of a personalised cancer vaccine. The vaccine aimed to train each patient’s immune system to recognise tumour cells remaining after surgery, while Keytruda helped the immune system find and attack cancer cells.

What did the phase 3 trial find?

All 1,137 adults received Keytruda. About two-thirds also received Intismeran, the experimental vaccine, while the rest received a placebo. The international trial included patients treated at Addenbrooke’s Hospital in Cambridge.

Researchers reported three linked outcomes:

• The combination lowered the risk of death or melanoma returning by 42%.
• It reduced the risk of melanoma spreading by 38% over two years compared with Keytruda alone.
• At two years, 82.2% of patients receiving Intismeran plus Keytruda remained cancer-free, versus 70% among those receiving Keytruda alone.

That last comparison represents a 12.2 percentage-point difference, or roughly 12 additional cancer-free patients per 100 treated.

The practical takeaway: The vaccine added a sizable two-year difference to immunotherapy; it remains an add-on in this study.

How did Intismeran train the immune system?

Intismeran was personalised for each patient and used cells from that patient’s tumour to train the immune system to identify melanoma cells needing attack. It was given as an mRNA jab alongside Keytruda.

Professor Pippa Corrie, a consultant medical oncologist who helped run part of the study at Addenbrooke’s, said: “The personalised cancer vaccine uses exciting technology to stimulate the patient’s own immune system to recognise and attack any tumour cells remaining after surgery.”

She added: “It is a whole new approach to cancer treatment, which is designed to improve outcomes compared with standard anticancer drug treatments that don’t take into account individual differences, and this trial was the first proof of principle.”

Because every patient’s cancer and immune system are different, treatment can be designed around the individual tumour’s genetic profile rather than one standard medicine.

The practical takeaway: Intismeran used the patient’s own tumour as the immune system’s training target.

What did trial participation mean for Tony Chapman?

Tony Chapman, 75, was diagnosed with stage 3 melanoma in 2019. The retired businessman from North Northamptonshire had a melanoma removed from his chest. Four years later, he found a lump under his armpit and needed surgery to remove the lymph nodes.

Chapman then joined the international trial at Addenbrooke’s. He completed treatment at the NIHR Cambridge Clinical Research Facility last year and remains cancer-free. He does not know whether he received Intismeran or a placebo alongside Keytruda.

“I couldn’t get over how groundbreaking it sounded,” Chapman said. “The opportunity to play a small part in furthering scientific research, potentially helping others along the way, was too exciting to miss out on.”

The practical takeaway: Chapman remains cancer-free, but he cannot know whether the vaccine helped him personally.

Can the approach work in other cancers?

Drug manufacturers MSD and Moderna said the combined approach is now being tested in kidney, bladder and lung cancers. That company statement describes studies in progress; it does not establish that the melanoma results carry over to those cancers.

Cancer experts outside the study were impressed but called for more trials. Professor Alan Melcher, professor of translational immunotherapy at The Institute of Cancer Research in London, said: “Melanoma is leading the way, but vaccines are being investigated in many other cancers, including cancers that are very difficult to treat and don’t respond well to current immune-based treatments.”

“The challenge now is working out which cancers and which patients are most likely to benefit, and which are the best vaccine targets to go for,” Melcher added. Further studies must also establish which treatments help patients live longer.

“We’re closer to cancer vaccines becoming part of routine treatment than we’ve ever been, but they are not going to replace existing treatments across the board,” Melcher said. “The more realistic prospect is that they become another powerful tool that we can combine with treatments such as immunotherapy.”

The practical takeaway: Other-cancer studies are underway, but melanoma data cannot yet predict results in kidney, bladder or lung cancer.

What could personalised cancer vaccines change?

Dr Lennard Lee, associate professor of AI and cancer vaccine research at the University of Oxford, called the result “a major breakthrough for cancer vaccine research.” He added: “Perhaps the biggest implication is that the future of cancer vaccines may be personalised. Every patient’s cancer is different. Every person’s immune system is different.”

“Rather than giving everyone the same medicine, this trial demonstrates the potential of designing cancer vaccines around the unique genetic fingerprint of an individual patient’s tumour,” Lee said.

The report describes melanoma as the most aggressive form of skin cancer, with about 2,600 deaths each year in the UK. Only around one in three patients with the worst form of the disease are alive five years after diagnosis.

The practical takeaway: Personalisation may become one powerful tool within cancer care, and the next test is whether Intismeran’s two-year benefit persists, improves overall survival and carries into other cancers.