5 things you should know about intismeran, the Moderna-Merck cancer vaccine

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The phase 3 results for intismeran autogene, the “cancer vaccine” for melanoma, that were presented at the European Society of Medical Oncology made headlines and stirred up social media traffic around the world late last week and over the weekend. Here are five things you should know about the treatment and the recent flurry of news coverage about it.

News of the positive phase 3 results was released last week after an embargo violation

Results of the trial of the vaccine, intismeran autogene (which commonly get shortened to just intismeran) were scheduled to be released on Saturday at the ESMO meeting in Madrid, but Oncology Central, a cancer news site operated by Informa, a medical meeting and publishing company based in London, broke the embargo. Because the news of the trial, Moderna, the Cambridge, Massachusetts-based company that developed intismeran, and Merck, the developer of Keytruda (pembrolizumab), the well-established immunotherapy drug that is given with experimental intismeran, hurried up and issued a news release on Oct. 22 (last Thursday) at 2:59 p.m. ahead of the planned presentation of the data at ESMO, which occurred on Saturday as scheduled.

Moderna’s stock price plunged after the news release despite the positive results. Why?

News reports on the study results trumpeted the positive results for the intismeran-Keytruda combination and the novelty of what is being called a cancer vaccine. Even so, Moderna’s share price plunged by 21% on Oct. 22. The share price recovered somewhat by the time the NASDAQ exchange closed on Friday. Merck’s stock price also nosedived. The headline on the Wall Street Journal’s story on Friday read. “Moderna’s Cancer Success Doesn’t Live Up to Early Hype.” The newspaper reported that the disconnect between the upbeat headlines and the falling stock price stemmed from the higher expectations of investors, fed by some earlier positive results, and the related concern that the benefit of the intismeran-Keytruda combination isn’t large enough to offset the technical difficulty of delivering the intismeran and the expected price, which the Journal said would be $400,000 a year. Other news outlets cast intismeran as a fulfillment of the long-sought cancer vaccine.

There were some differences between the Phase 2b trial results presented at ASCO and the phase 3 results presented at ESMO

The phase 3 results presented at ESMO did not come out of nowhere. Results of a phase 2b trial were presented at the annual meeting of the American Society of Clinical Oncology (ASCO) in June 2026. As expected, the number of patients enrolled in the phase 2b trial was much smaller than in the phase 3 trial featured at ESMO (157 vs. 1,137), but phase 2b was much longer, with a median follow-up of 60.3 months compared with 24.3 months in the phase 3 trial

The researchers who conducted the study used recurrence-free survival as the primary end point. The recurrence-free survival rate in the intismeran-Keytruda group in the phase 2b trial at 60.3 months was 68.8% compared with 49.1% in the Keytruda alone group with a hazard ratio of .51, which translates into a risk reduction of 49%.

In the phase 3 trial, at the 24.6-month mark, the recurrence-free survival rate was 82.2% among the patients who received the intismeran-Keytruda combination compared with 70% in the Keytruda group, with the investigators reporting a hazard ratio of .58, which translates into a risk reduction of 42%, a notch or two less than the recurrence-free survival risk reduction reported by the phase 2b trial investigators.

The difference in the risk reduction in distant metastasis-free survival between the two trials was larger and drew more notice. Phase 2b investigators reported a risk reduction in the distant metastasis-free survival end point at ASCO of 59%. The phase 3 investigators reported a risk reduction in the distant metastasis-free survival of 38% (88.5% in the intismeran-Keytruda vs. 80.2% in the Keytruda alone group, with a hazard ratio of .62).

Intismeran is considered a vaccine because it attacks cancer by generating a T cell response

In an infectious disease context, vaccines are typically understood to prevent infection with a disease-causing microorganism or, if an infection occurs, to significantly reduce its severity and to do so by priming the immune system to recognize and attack the microorganism.

Intismeran is preventing recurrence, not infection. It is framed as a vaccine because it is designed to prevent recurrence by recruiting the immune system’s T cells to attack cancer.

But unlike the infectious disease vaccines, intismeran is tailor-made to each patient and their cancer. As described in the new release about the phase 3 trial (a variety of news accounts add some color and explanation) intismeran is made using a tissue sample of the patient’s resected melanoma as well as healthy tissue. Algorithms identify up to 34 “neoantigens” that are unique to that patient and their cancer — described as the “mutational signature” in the news release from Moderna and Merck. That information is used to make synthetic RNA that is injected into the patient. The synthetic RNA then encodes the neoantigens that train the patient’s T cells to recognize and pounce on any melanoma cells bearing that mutational signature, thereby stifling a recurrence.

Calling intismeran a cancer vaccine is catchy and makes some sense, but it lacks precision. Moderna and Merck are describing their novel treatmen a potential first-in-class “individualized neoantigen therapy,” or INT.

Moderna and Merck are not stopping at melanoma

For cancer drug developers, especially those looking to develop bespoke treatments, melanoma has the advantage of tissue samples that can be easily accessed. But in the news release last week, Merck and Moderna said their “INTpath” program comprises nine phase 2 and phase 3 trials, including three phase 3 trials for non-small lung cancer and a phase 1 trial of intismeran as a treatment for pancreatic ductal adenocarcinoma.