Suck on that melanoma.

An Aussie cancer fighting legend has helped us take another step to conquering the cancer with a particularly nasty Aussie angle.

(First published on my Substack where you can get #NerdNews, marvellous maths and general geekery.)

(Georgina Long, total Boss! courtesy Tim Bauer)

mRNA has a new gig.

When most of us hear mRNA vaccine, there’s a fair chance our minds wander back to 2021, to lockdowns and to somebody yelling at us on Facebook.

Quick reminder for those of us trying to forget 2020–23.

Traditional vaccines usually show your immune system a harmless piece, or a weakened or inactive version, of a pathogen. That piece is most often one of its surface proteins, sometimes a sugar from its coat. It won't make you sick, but it is enough to make your body recognise the invader and build a coalition of antibodies and memory cells, leaving you ready to clobber the real thing later.

An mRNA vaccine skips supplying the protein itself. It gives some of your cells temporary genetic instructions for making it and your immune system goes to work.

Well, mRNA has a new gig.

Moderna and Merck have announced that their personalised mRNA treatment intismeran, used with the immunotherapy drug Keytruda, has beaten Keytruda alone in a Phase III trial involving 1,137 melanoma patients.

Yes melanoma. That horrible and horribly Australian cancer. A legacy of our sun-loving, fun-loving outdoor ways. A cancer that until recently had stubbornly resisted all efforts to best it.

Well it looks like we’ve kicked melanoma in the goolies again. And this time we are going all the way, with mRNA.

The trial that’s making them smile.

They research focussed on people with high-risk melanoma whose tumours had already been surgically removed. The problem is always that in removing the visible cancer you can’t 100% guarantee that a few cells haven’t escaped and set themselves up somewhere else.

So does adding the vaccine to the Keytruda stop the melanoma coming back? And does it stop it spreading to distant parts of the body?

According to Moderna and Merck, that’s a big yes on both counts.

A little bit of history. The first positive Phase III result for a personalised mRNA cancer vaccine.

“Today’s results represent a landmark moment for adjuvant* melanoma treatment.” — Professor Georgina Long, Melanoma Institute Australia, Clinical Lead.

Recognise the name? Yep THAT Georgina Long. 2024 Australian of the Year and absolute bloody legend.

So what’s the hot shot got?

Now this isn’t a vaccine that stops you getting melanoma in the first place. It is created, and does its work, after you get cancer. And the cool bit: it is made specifically for your cancer.

Doctors take a sample of the tumour and sequence it, looking for mutations that are present in your cancer cells but not your normal cells. From those they select up to 34 targets, called neoantigens, that look useful for getting the immune system’s attention.

Moderna then makes an mRNA treatment carrying the instructions for those targets.

Once injected, some of your cells read the mRNA and make the relevant proteins. Your immune system looks at those proteins and, in the ideal case, learns that cells displaying those mutations are trouble.

Which is where the Keytruda comes in, along with our most awesome T-cells.

T-cells, you might remember from previous NerdNews, are a type of white blood cell that act like soldier cells in your body. They find and destroy germs like viruses, and they tell other parts of the immune system how to carry the fight.

Well T-cells have built-in brakes to stop them attacking everything in sight. One of those brakes involves a protein called PD-1. Unfortunately cancers have evolved ways of exploiting that system and effectively telling T-cells to settle down and leave them alone.

Keytruda blocks PD-1.

So, very roughly, the vaccine helps tell the immune system what to look for and Keytruda blocks the cancer’s ability to tell your immune system, ‘hey leave me alone here, we’re all cool yeah?’.

“That principle can now be applied to cancer, and that’s a big advance.” — Dr Eliav Barr, Merck Chief Medical Officer.

We have been here before. Sort of.

These findings it builds upon an earlier trial that was already pretty impressive.

A randomised Phase IIb study involved 157 people with high-risk melanoma. At 18 months, 79% of those given the personalised vaccine plus Keytruda had avoided recurrence, compared with 62% on Keytruda alone.

Longer follow-up has made that result look even better. At five years, the combination reduced the risk of recurrence or death by 49%, and the risk of distant metastasis or death by 59%, compared with Keytruda on its own.

What has changed this week is the scale of the evidence.

“This is an auspicious start — this is where things begin.” —Karen Knudsen, Parker Institute for Cancer Immunotherapy.

Reality bites.

Now before we declare the war on melanoma over, we need to take a breath.

The excitement is understandable, especially when dealing with such a brute of a disease, but bear in mind a few things.

We don't actually have the detailed Phase III numbers yet.

Moderna and Merck say the improvement was statistically significant and clinically meaningful, but they haven't released the recurrence rates, hazard ratios or event counts.

Professor Long is due to present the full results at the European Society for Medical Oncology Congress in Madrid, which runs from 23 to 27 October. At the time of writing, the exact session has not been announced.

We don’t yet know whether the treatment helps people live longer. Overall survival is still being followed. Same for side effects.

And even if this works as well as everyone hopes, making it is far more challenging than off-the-shelf vaccines.

You can’t simply manufacture a few million identical doses. Each patient’s tumour has to be sampled and sequenced. That person’s individual mutations must be analysed, their targets chosen, and a unique vaccine created.

Regardless, given that roughly 17,000 Australians are diagnosed with melanoma each year, this is certainly a step in the right direction.

And melanoma isn’t the only game in town. M&M are already testing personalised cancer vaccines in other tumours, including lung, kidney and bladder cancers.

Some will almost certainly disappoint. Others? Who knows.

But take a moment to celebrate the genius of Long and her crew. After decades of going nowhere on melanoma, we now sit amidst an explosion of progress.

Go you good things!

Further Reading:

Peer-reviewed

• Weber JS et al., “Individualised neoantigen therapy mRNA-4157 (V940) plus pembrolizumab versus pembrolizumab monotherapy in resected melanoma (KEYNOTE-942): a randomised, phase 2b study,” The Lancet (2024): https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(23)02268-7/abstract

• Khattak A et al., “Intismeran Autogene Plus Pembrolizumab Versus Pembrolizumab Alone in High-Risk Resected Melanoma: 5-Year Update of the Randomized Phase IIb KEYNOTE-942 Study,” Journal of Clinical Oncology (2026): https://ascopubs.org/doi/10.1200/JCO-26-00835

• Rojas LA et al., “Personalized RNA neoantigen vaccines stimulate T cells in pancreatic cancer,” Nature (2023): https://www.nature.com/articles/s41586-023-06063-y

Reporting

• Reuters, “Moderna, Merck vaccine cuts recurrence and spread of melanoma, raising new treatment hope,” 19 August 2026: https://www.reuters.com/legal/litigation/merck-moderna-say-melanoma-skin-cancer-vaccine-meets-goals-large-trial-2026-08-19/

• Matthew Herper and Angus Chen, “Moderna and Merck say mRNA cancer vaccine succeeded in late-stage melanoma trial,” STAT, 19 August 2026: https://www.statnews.com/2026/08/19/mrna-cancer-vaccine-trial-melanoma-merck-moderna/

• Associated Press, “Moderna shares surge after it says its experimental mRNA cancer treatment passed a key test,” 19 August 2026: https://apnews.com/article/2330dce708b0af215b68570b19d025df