New Delhi: A personalised mRNA vaccine reduced the chances of high-risk melanoma returning or spreading in a Phase 3 trial, US-based pharma companies Moderna and Merck said Wednesday. The vaccine was given alongside Merck’s immunotherapy Keytruda to patients whose melanoma had been surgically removed.
The companies said the combination worked better than Keytruda alone, making it the first late-stage trial to show a personalised mRNA cancer vaccine can improve outcomes when added to an existing immunotherapy.
In this vaccine, mRNA—a molecule that carries instructions to cells to make proteins—helps train the immune system to recognise mutations in a patient’s cancer.
Moderna’s shares more than doubled following the results, while Merck’s stock also hit an all-time high, a Wall Street Journal report said Wednesday.
Moderna and Merck had begun collaborating to develop the personalised mRNA cancer vaccines in 2016.
The experimental mRNA vaccine, intismeran autogene, was tested in 1,137 patients with stage IIB-IV melanoma whose tumours had been completely removed through surgery. Patients received either intismeran with Keytruda, or Keytruda alone.
Melanoma is one of the deadliest forms of skin cancer because it can return after surgery and spread to other organs.
The interim results showed that the combination met its main goal of delaying cancer recurrence and its secondary goal of reducing the risk of cancer spreading to distant parts of the body, compared with Keytruda alone.
“Today’s results represent a landmark moment for adjuvant melanoma treatment,” said Professor Georgina Long, the study’s principal investigator and medical director of Melanoma Institute Australia.
She said the trial was the first Phase 3 study to show that intismeran, designed around the unique mutations of a patient’s tumour, could reduce the risk of recurrence or death when given with pembrolizumab.
Pembrolizumab, sold as Keytruda, is an immunotherapy drug that helps the immune system recognise and attack cancer cells.
For Moderna, these results could pave the way for its entry into the $240-plus-billion cancer-drug market, a boon for a company that has been dependent on Covid-19 vaccine sales, which have been falling.
Moderna has struggled to regain its financial footing as Covid-19 vaccine demand has declined, posting losses in the years since the pandemic peak, WSJ reported.
How the personalised cancer vaccine works
Unlike conventional vaccines, which are designed to protect against a virus or bacteria, this vaccine is made specifically for a patient’s cancer.
After surgery, doctors analyse a sample of the patient’s tumour and blood to identify mutations unique to the cancer. Scientists then select mutations that are most likely to trigger an immune response and encode them into mRNA.
The mRNA carries instructions that teach the immune system to recognise these cancer-specific targets. If cancer cells carrying those mutations remain in the body, immune cells can identify and attack them.
The vaccine takes about six weeks to manufacture after the tumour biopsy. During this period, patients can begin treatment with pembrolizumab to help keep the cancer in check.
The vaccine is then given alongside pembrolizumab. The immunotherapy helps the immune system stay active against cancer cells, while the vaccine gives it specific targets to recognise.
In earlier research, the combination had already shown promise. A five-year follow-up from the Phase 2b trial showed a 49 percent reduction in the risk of melanoma recurrence or death compared with Keytruda alone.
What the Phase 3 trial showed
Patients in the trial were randomised in a 2:1 ratio to receive either intismeran alongside pembrolizumab, given for up to nine doses over about a year, or pembrolizumab alone.
The trial met its primary goal of improving recurrence-free survival, which measures how long patients remain free of cancer after treatment.
It also met its key secondary goal of improving distant metastasis-free survival, meaning patients receiving the combination were less likely to have the cancer spread to distant parts of the body.
Both results were significant.
The companies have not yet released detailed data on how long patients remained free of cancer or whether the treatment improved overall survival. The full results are expected to be presented at a medical meeting later this year, WSJ reported.
The result is important because personalised cancer vaccines have long been proposed as a way to make the immune system target mutations specific to an individual’s tumour.
“These Phase 3 findings represent a pivotal moment for the field of cancer research,” said Moderna CEO Stéphane Bancel. “For many years, the idea of creating an mRNA treatment designed specifically for an individual patient’s cancer was aspirational. We are now helping turn that vision into a reality.”
Moderna and Merck said they now plan to discuss the results with regulators and present full data at an international medical meeting.
But the treatment remains experimental. Researchers will need to assess the full data, including how long the benefit lasts, overall survival and safety.
There is also a practical challenge. Unlike conventional vaccines manufactured in large batches, a personalised cancer vaccine has to be designed and produced for each patient.
(Edited by Sugita Katyal)