An innovative skin cancer treatment combining immunotherapy and mRNA vaccine technology has delivered promising results in a late-stage trial, the pharmaceutical companies Merck and Moderna said in a news release Wednesday.
The experimental treatment performed better than immunotherapy alone in reducing the recurrence of melanoma, and in restricting the spread of the cancer to other parts of the body in patients who had previously undergone surgery for melanoma, the news release said.
The announcement about the treatment, called intismeran, said the results showed “statistically significant and clinically meaningful improvements.”
Doctors reacted to the announcement with guarded enthusiasm: the Phase 3 trial — the last stage before seeking regulatory approval — is not yet complete and the results announced Wednesday come from an interim analysis.
The companies say they will later present data at an oncology conference and share it with regulators.
‘It’s still early’
But even as doctors await full details, Dr. Marcus Butler, a medical oncologist and melanoma disease site lead at Toronto’s Princess Margaret Cancer Centre, called the announcement an exciting development for the field.
The Phase 2 study of the treatment had previously shown promising results with a much smaller number of people in the trial, Butler said. That means positive results in a larger Phase 3 trial are cause for optimism.
“We’re really hopeful that the magnitude of benefit will be substantial, but it’s still early,” Butler said.
Once finalized, if the complete trial data do confirm the results, the timeline to the treatment being available to Canadians is likely more than eight months away, said Dr. Ramy Saleh, an associate professor of oncology at Montreal’s McGill University.
“The biggest challenge in all of this is, how do you go from a small clinical trial of a handful of patients and do a worldwide expansion?” Saleh said.
He said government, health-care officials and industry will need to solve logistical and operational problems to roll out a novel treatment at scale.
“The million-dollar question is, how much will this cost?” he said.
Another key question, he added, is whether taxpayers and governments are willing to get on board.
According to the Canadian Cancer Society, around 11,300 people in Canada are likely to be diagnosed with melanoma this year, and an estimated 1,250 people will die from it. Melanoma Canada says melanoma is one of the most common types of cancer found among Canadians aged 15 to 29 and 30 to 49.
“We are still losing three people every day in Canada to melanoma,” said Falyn Katz, CEO of Melanoma Canada. “So if this can help with that, then that’s a big win.”
Butler noted that public companies often announce early findings to satisfy market disclosure rules and prevent insider trading, rather than holding the data until the study finishes. Shares of Moderna closed up almost 177 per cent in Wednesday trading, while Merck closed up 12.6 per cent.
‘Recognize and attack’
The treatment combines Merck’s immunotherapy drug pembrolizumab, sold as Keytruda, with a made-to-order mRNA vaccine from Moderna that is based on an analysis of mutations found in the patients’ own tumours.
The immunotherapy effectively stimulates the immune system by unblocking its “checkpoints,” Butler said. Messenger-based RNA vaccines, meanwhile, give our cells instructions to help the immune system fight a pathogen or other foreign substance, including cancer cells.
Merck’s immunotherapy drug pembrolizumab, sold as Keytruda, effectively removes constraints on the immune system. (Michael Lund/Merck/The Associated Press)
In comments published on Science Media Centre UK, Dr. Lennard Lee, a consultant medical oncologist and associate professor at Oxford, said this treatment uses tumour samples to single out abnormal proteins in cancer cells — called neoantigens. An mRNA vaccine created from an individual patient’s tumour samples can then train their immune system “to recognize and attack cancer cells” carrying those antigens.
“In simple terms, one treatment helps show the immune system what to look for, while the other helps release the brakes on the immune response,” said Lee.
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Caveats and limitations
The trial enrolled 1,137 high-risk patients with Stage IIB-IV melanoma that had been surgically removed. Canadian patients were among those in the trial, Butler said, including several at Princess Margaret.
Volunteers were randomized to receive up to nine doses of Keytruda plus the personalized vaccine or Keytruda alone for about one year. The companies said no new safety signals have emerged in the trial.
One concern about the study, Butler said, is that mRNA vaccines in general can stimulate the immune system, even without specific engineering to combat melanoma neoantigens. COVID-19 mRNA vaccines, for example, have been linked to higher cancer survival rates when given while a patient was undergoing immunotherapy.
Because patients who received a placebo did not receive a “dummy vaccine,” Butler said, the study may not fully distinguish between positive results from general mRNA immune stimulation and results due to the specific mRNA melanoma vaccine.
Butler also cautioned that this trial’s focus was limited only to patients at the early stage of melanoma whose tumours were completely surgically removed. Other clinical trials are under way for patients with later-stage melanoma, he said — and some past studies have had negative results.
“So just because this approach may work in the early stage does not necessarily mean it’ll work in later stages,” he said. “Time will tell and these studies need to happen.”