This is the 'best proof of concept we’ve had of a cancer vaccine', says a leading Australian oncologist.
An mRNA cancer vaccine has shown what the manufacturer, Moderna, says are significant improvements in survival rates for patients at high risk of recurring melanoma.
The phase IIb trial results showed that adjuvant therapy combining an investigational personalised mRNA cancer vaccine developed by Moderna and anti-PD-1 therapy, pembrolizumab (Merk’s Keytruda), reduced the risk of recurrence or death by 44% compared with treatment with the anti-PD-1 therapy alone for patients with stage III/IV melanoma.
“These data provide the first evidence that we can improve on the rates of recurrence free survival achieved by PD-1 blockade in resected high-risk melanoma,” Moderna chief executive Stephane Bancel said in a statement.
“You’d have to feel pretty bullish about the likelihood that this combination will eventually show the sort of overall survival improvement we’re all gunning for, but time will tell.”
Professor Mark Shackleton
The trial involved 157 patients with stage III/IV melanoma who had surgical resection. They were randomised to receive either adjuvant therapy – nine doses of the mRNA vaccine and 200mg of the anti-PD1 therapy every three weeks for around a year – or monotherapy with the anti-PD1 blockade for around a year or until the tumour recurred or toxicity was too high.
Professor Mark Shackleton, director of oncology at Alfred Health, told The Medical Republic he would be surprised if the vaccine didn’t change practice down the track.
“It feels like it’s the best proof we’ve had of the concept of cancer vaccination,” he said.
“That to me is almost the most exciting part, because it empowers a whole field of research investment to really explore the potential of this approach.
“Hopefully this is the spark that will light the flame around this concept.”
“The whole field of cancer vaccination is a fantastic concept and you feel it’s just got to work. But for much of the last 20 or 30 years it hasn’t really worked.”
Professor Mark Shackleton
Pembrolizumab alone has already been shown to have substantial benefits in terms of relapse-free survival and the additional benefit with the mRNA vaccine was substantial, said Professor Shackleton.
“So you’d have to feel pretty bullish about the likelihood that this combination will eventually show the sort of overall survival improvement we’re all gunning for, but time will tell,” he said.
Professor Shackleton said the concepts were being tested as far back as the 1990s when he was working on cancer immunotherapy studies.
“The whole field of cancer vaccination is a fantastic concept and you feel it’s just got to work. But for much of the last 20 or 30 years it hasn’t really worked,” he said.
However, the relatively new techniques of using tailor made messenger RNA derived from a patient tumour to create personalised vaccines provided a proof concept, he said.
“It’s wonderful to see that as the decades have rolled on and technology has improved that those visions might now start to become realised,” he said.
There are caveats of course. The study was small and it was still early days, said Professor Shackleton.
Adjuvant immunotherapy trials to date have seen good results with respect to the endpoint of recurrence-free survival, he explained.
“But they haven’t yet met the arguably higher bar endpoint of improvement in overall survival,” he said.
“Although no-one doubts the ability of adjuvant immunotherapy to prevent relapse disease, it’s not 100% clear that that translates into an increased chance of actually being alive, for example, five years after the treatment, so it’s still it’s still an evolving field.”
The vaccine could be explored as a way to augment immunotherapy treatment for hard-to-treat melanomas, such as mucosal and choroidal, said Professor Shackleton.
Those types of sub-cancers are thought to be less immunogenic than those occurring on the skin, so immunotherapy hasn’t been quite as effective.
“The possibility that you might increase the chance that the immune system would recognise those sorts of wonky genes and proteins as being abnormal, and such that an immune response is elicited with vaccines is certainly a very appealing approach for those types of cancers,” he said.
