A new study showed that an investigational individualized mRNA vaccine for surgically resected melanoma demonstrated durable benefits in reducing the risk of recurrence and distant spread in a 5-year follow-up. The new mRNA vaccine, from Moderna and Merck, had previously shown promising results in treating and preventing recurrence of melanoma when used with the drug Keytruda (pembrolizumab), a cancer immunotherapy treatment. This is more good news regarding the usefulness of mRNA vaccines in the war on cancer.

The mRNA vaccine technology allows clinicians to create individualized vaccines to assist in treating cancer in conjunction with surgery and chemotherapy.

This post will examine the new results for the melanoma mRNA vaccine.

About the melanoma mRNA vaccine

The approach with intismeran (formerly V940 or mRNA-4157) vaccine aims to strengthen existing T-cell activity and create new antitumor T-cell responses. The vaccine can encode up to 34 personalized neoantigens encapsulated within a lipid nanoparticle and, for manufacturing, requires a 1 mm³ tumor sample from patients for neoantigen identification via next-generation sequencing.

The mRNA vaccine for melanoma is individualized; that is, each person receives an mRNA vaccine engineered to match their unique cancer cells. The mRNA melanoma vaccine developed for person X will probably not work in person Y.

I need to make an important point — cancer “vaccine” is a bit of a misnomer. These vaccines induce an immune response for treating melanoma, but they do not prevent the disease. Although we call them “vaccines,” they act more like immunotherapy.

This mRNA vaccine is individualized, meaning it codes for antigenic proteins on each person’s melanoma cells. Every person has slightly different antigens, even if they have the same cancer type. However, this vaccine may provide immunity to a recurrence of the cancer, so, in a sense, it is also preventative.

So, how does this “vaccine” work? The mRNA cancer vaccine trains the immune system to attack cancer cells that may have been missed by surgery or chemotherapy, or have metastasized to another location. But, and this is important, it probably would not affect another type of tumor. For example, this melanoma mRNA vaccine will probably be useless against colorectal cancer.

In the case of this new mRNA-based melanoma vaccine, it is given after surgery and during chemotherapy using Keytruda.

mRNA-based melanoma vaccine study

In a study published on 1 June 2026 in the Journal of Clinical Oncology, Matteo Carlino, MD, PhD, University of Sydney, Australia, and colleagues, studied a phase IIb trial randomized 157 patients with resected stage IIIB-IV melanoma in a 2:1 ratio to either intramuscular intismeran autogene (up to nine doses) plus IV pembrolizumab (up to 18 doses) every 3 weeks or to pembrolizumab alone, with treatments continued until progression or unacceptable toxicity.

Pembrolizumab was started within 13 weeks of surgery, and patients needed to have sufficient tumor tissue available to allow for the design of intismeran.

Participants had an average age of about 60 years, over 60% were men, and more than 85% had stage IIIC-D cancers.

Here are the key results:

• At 4 years, absolute rates of recurrence-free survival (RFS) and distant metastasis-free survival (DMFS) with the addition of the neoantigen vaccine improved by roughly 20% compared with pembrolizumab alone:
  • RFS: 72.4% vs 49.1%
  • DMFS: 83.9% vs 65.4%
• Intismeran plus pembrolizumab continued to prolong RFS (49% lower risk) and DMFS (59% lower risk) at five years.

There were no new safety signals from intismeran with longer-term follow-up. Treatment-related adverse events (AEs) were reported in all patients in the combination arm and 84% of the pembrolizumab arm. Most AEs were low-grade and included fatigue, injection-site pain, fever, and chills. Grade 3 adverse events related to intismeran occurred in 10.6% of participants.

The researchers concluded:

After 5 years’ follow-up, intismeran plus pembrolizumab demonstrated sustained, durable treatment benefits versus pembrolizumab alone in resected high-risk melanoma.

Summary

This is more good news about the power of mRNA vaccines in treating cancer. Unfortunately, we have a lot of people who don’t understand how mRNA vaccines work and will think it’s doing something nefarious to the body. It’s not — it’s helping to kill cancer cells.

I think mRNA vaccines will be at the forefront of tools that can help conquer cancer. I am optimistic, unless the anti-mRNA vaccine crowd stops all research on them.

For now, we are getting great results from these vaccines, and I hope that they become the standard of treatment for many cancers.

Citations

• Khattak A, Carlino MS, Meniawy T, Ansstas G, Taylor MH, Kim KB, McKean M, Long GV, Sullivan RJ, Faries M, Tran TT, Cowey CL, Pecora A, Medina T, Atkinson V, Krepler C, Jemielita T, Mao H, Chow J, Ojalvo LS, Mehnert JM. Intismeran Autogene Plus Pembrolizumab Versus Pembrolizumab Alone in High-Risk Resected Melanoma: 5-Year Update of the Randomized Phase 2b KEYNOTE-942 Study. J Clin Oncol. 2026 Jun 1:101200JCO2600835. doi: 10.1200/JCO-26-00835. Epub ahead of print. PMID: 42223134.

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