Clinical trial results for a new melanoma vaccine are promising, but UNSW Sydney experts say key questions still need to be answered.
On 13 December 2022, Moderna and Merck shared findings about a new mRNA-based vaccine for melanoma, labelled in the media as ‘the penicillin moment’ for cancer treatment. Initial results from their KEYNOTE-942 clinical trial show that the vaccine, developed by Moderna, significantly reduced the risk of cancer recurrence or death for melanoma patients.
“Melanoma vaccines have been worked on for decades, albeit with little efficacy. However, this is one of the first that has shown promising enough results to proceed to a larger definitive study,” said Professor Anthony Joshua, who is a medical oncologist and Head of Clinical Science at the Garvan Institute of Medical Research, as well as a Conjoint Professor at UNSW Medicine & Health.
How does the melanoma vaccine work?
Historically, we have developed vaccines against infectious microorganisms, which cause diseases like polio and COVID-19. The vaccines prime our immune system to fight off these microorganisms if we encounter them in the future.
Cancer, on the other hand, is not generally infectious. The disease occurs when our own cells develop genetic mutations, start to behave abnormally and multiply rapidly to form tumours. However, along with clearing out microorganisms like viruses and bacteria, our immune system is also able to recognise tumour cells and remove them from the body. Tumour cells have mutated components that differentiate them from normal cells – and this is especially true for melanoma.
“Melanoma is a highly mutated cancer – so there are often ‘foreign’ parts to the cancer that the immune system can attack,” Prof. Joshua said.
Therefore, a melanoma vaccine generates an immune response to the foreign components of the tumour cells. This enables the immune system to better control the tumour.
Who would get the melanoma vaccine?
It all sounds exciting, but don’t be lining up for your pre-summer shot. This vaccine is designed for patients with existing melanoma, to prevent the tumour from coming back after it has been surgically removed.
Also, the vaccine is personalised to each patient. Why? Each patient’s melanoma contains different mutated components. It’s necessary to understand which components the immune system can recognise and attack to include within the vaccine.
“The Moderna vaccine currently being discussed targets a number of tumour mutations which are highly specific to the individual being treated. [These mutations] are analysed and chosen to give the greatest immune response and developed into a vaccine which is personalised for the patient,” said Dr John Frew, who is a dermatologist at Liverpool Hospital and Conjoint Senior Lecturer at UNSW Medicine & Health.
Unfortunately, a common melanoma vaccine is unlikely to be effective due to individual differences between patients.
“Each melanoma has a large number of genetic mutations that are distinct from normal skin tissue. As a result, melanomas from two people are likely to be genetically quite divergent,” said Dr Sarah Sasson, who is a Clinical Immunologist/Immunopathologist and Scientia Senior Lecturer at the Kirby Institute at UNSW.
“This means making a 'one size fits all' melanoma vaccine might have a low overall efficacy in a large number of patients living with melanoma.”
What do Moderna and Merck’s clinical trial results mean?
The Phase 2 clinical trial involved 157 patients with advanced melanoma which had been surgically removed. For these patients, there was a risk that the melanoma had metastasised and would recur in other areas of the body. One group of patients received the melanoma vaccine and Merck’s immunotherapy drug Keytruda, with the other group receiving just Keytruda. Treatment with the vaccine reduced the risk of cancer recurrence or death by 44 per cent.
“It’s certainly exciting… But these are early results and the trial is quite small, and this concept needs to be tested further. It will also be important to see how and if the vaccine did indeed generate an immune response against the tumour and how long it lasts,” Prof. Joshua said.
In 2023, Moderna and Merck plan to submit the full results from KEYNOTE-942 for peer review and publication. They also plan to initiate a Phase 3 clinical trial, which may bring this much-needed treatment closer for melanoma patients.
“It is an excellent step in the right direction using new personalised medicine technology, which has come to us as a silver lining out of the COVID-19 pandemic and experience with mRNA vaccines,” Dr Frew said.
“It certainly opens up new doors to novel therapeutics and novel adjuvant therapies – but it is as yet unclear whether this is a true ‘penicillin moment’.”
Note: the experts quoted in this article were not involved in the KEYNOTE-942 clinical trial and are commenting as external experts.