Reuters (“Success after a century of failures: Inside Moderna and Merck’s cancer vaccine breakthrough“):

Stephane Bancel, CEO of Moderna, was at a Lebanese restaurant celebrating a friend’s birthday late on August 13 when he got the call.
An mRNA cancer vaccine the company had been developing with Merck had hit its mark — the first success of a therapeutic cancer vaccine in late-stage testing after more than 100 years of failed attempts.

Cancer experts hailed it as the beginning of an era of custom-made vaccines that train the immune system to ​fight an individual patient’s cancer. In a trial of more than 1,000 patients with localized melanoma, the vaccine kept tumors from coming back or spreading.
With full trial details pending, Wall Street is already estimating ‌billions of dollars in sales.

[…]

For Merck and Moderna, it was a moment built over 10 years, according to ⁠eight current and former company executives. When they announced a partnership in 2016 to develop a cancer vaccine, the companies had been working for over a year on a separate vaccine venture. For the cancer collaboration, Merck paid $200 million upfront in 2016 ​and another $250 million in 2022. The companies share costs and profits.

At that time, Merck’s Keytruda was emerging as a powerhouse in a new class of drugs called checkpoint inhibitors that could unleash the immune system to fight cancers by removing a natural ​brake. At that time, Merck’s Keytruda was emerging as a powerhouse in a new class of drugs called checkpoint inhibitors that could unleash the immune system to fight cancers by removing a natural ​brake. “What Keytruda taught the world was that, yes, there is an immune recognition of cancer, but cancer is clever in putting up barriers, and Keytruda removes those barriers,” Merck’s Barr said during an interview in late May.

[…]

Tal Zaks, who served as Moderna’s chief medical officer from 2015-2021, immigrated to the U.S. from Israel in 1996 to work on cancer vaccines at the National Cancer Institute. “We ​failed back then, and we failed for many years,” Zaks said. But he thought new technologies based on mRNA plus checkpoint inhibitors, as well as cheaper genetic sequencing, might open a path toward success.

Moderna had the mRNA technology, but as a ​young company, expensive cancer trials were out of reach. Bancel said Moderna spoke with companies that had checkpoint inhibitors, but knew Merck well and was swayed by its experience mounting Keytruda trials. Keytruda, which Merck’s Li calls a “miracle drug,” is used against 20 different kinds of ‌cancerous tumors and ⁠45 types and stages of cancer. But exactly what aspects of the tumor the drug targets, and why some patients respond better than others, remains a mystery.

[…]

The vaccine, known as intismeran autogene, trains the immune system to attack cancer cells by targeting mutations unique to each patient’s tumors. Prior cancer vaccines that attempted to train the immune system to target one or two specific tumor mutations failed.

The companies decided to test the vaccine in melanoma, which has among the highest number of mutations of any cancer and against which checkpoint inhibitors had a record of success. They also ​decided to test it in patients with early-stage melanoma following ​surgical removal of their tumors. That gave the companies ⁠critical time to create a customized vaccine based on a patient’s tumor and additional time for their immune systems to respond.

With mRNA technology, the companies were able to target dozens of mutations. “You have many, many more shots on goal and therefore a much greater chance to succeed,” Moderna co-founder and MIT scientist Robert Langer said via email.

The companies paired the vaccine ​with Keytruda’s ability to activate the body’s immune system T-cells that hunt down abnormal cells.
“The whole special thing about Keytruda was that it would unlock the dogs of war,” ​Li said. The vaccine provides 34 patient-specific ⁠cancer targets for those dogs to recognize, he said, and only one needs to work. “With the personalized cancer treatment, the dog has your scent.”

Both companies stand to benefit significantly if the vaccine is approved. U.S. approval could come as soon as next year.

U.S. Health Secretary Robert F. Kennedy Jr. has criticized the safety and efficacy of ⁠mRNA vaccines for ​infectious disease, without evidence, and cut $500 million in related projects.

But of course.

Writing for Nature, oncologist Patrick A. Ott urges, “The Moderna cancer vaccine offers hope — now we must speed up personalized therapies.”

The announcement on 19 August that people with melanoma who received a personalized vaccine lived longer without a cancer recurrence than those who didn’t have the vaccine is a sensation for the field. The results from pharmaceutical companies Merck, in Rahway, New Jersey, and Moderna, which is headquartered in Cambridge, Massachusetts, also made a big splash among researchers and people with cancer more widely.

What makes the findings so exciting and important is that they came from a large, late-stage phase III trial — a double-blind, placebo-controlled test involving more than 1,100 participants. It comes after a successful phase II trial in 2024, with just 157 participants (J. S. Weber et al. Lancet 403, 632–644; 2024). This latest study gives greater confidence that the vaccine, called intismeran, works, and brings it a step closer to gaining regulatory approval.

If intismeran is approved, it will become the first cancer vaccine available for people with melanoma and only the second therapeutic cancer vaccine, following the US Food and Drug Administration’s approval in 2010 of sipuleucel-T for advanced prostate cancer.

And the implications are wider. Because all cancers involve mutations in a cell’s DNA, personalized cancer vaccines, which target mutations that are specific to a tumour, could have broad applicability across cancers. Several phase II and phase III trials testing intismeran in people with melanoma, lung cancer, bladder cancer and kidney cancer are ongoing. And previous clinical trials testing other personalized vaccines have also had encouraging results.

The promise that cancer vaccines could soon be in use will lead to renewed interest and investment, accelerating discovery and advancing the field. The concept is attractive, being analogous to vaccination against infectious diseases. And there are ample opportunities to enhance cancer-vaccine efficacy further.

This is all incredibly exciting news. I’m rather shocked at how little attention it’s generating. I’m a rather avid follower of the news, checking multiple major sites daily, and somehow am just finding out about the breakthrough this morning.

That there’s a decent chance the drug won’t be approved because a wildly unqualified zealot is heading up our health department is deeply frustrating. It’s bad enough that he was able, unilaterally, to cut $500 million (a mere 0.0068% of the federal budget) in Congressionally appropriated funds from investing in this vital research.