Scientists are excited about recent trial results involving mRNA treatment for melanoma, which although less common than some other skin cancer types, is considered to be the most serious form, mainly because of its ability to spread to other organs more rapidly without early intervention, reports Medical News Today.
While treatment can remove or destroy the cancer, it is not uncommon for melanoma to recur, usually coming back within five years of treatment. Current treatments often include immunotherapy drugs like Keytruda (pembrolizumab), which helps the immune system recognise and attack cancer cells.
Now, trial findings presented at the recent 2026 American Society of Clinical Oncology (ASCO) Annual Meeting in Chicago suggest a combination of a personalised mRNA cancer vaccine developed by Moderna and used alongside Merck’s Keytruda may significantly reduce the chances of melanoma spreading after surgery, reducing the risk of distant metastasis by 59% over five years compared with Keytruda alone.
The results were also published in the Journal of Clinical Oncology.
How the vaccine works
The experimental vaccine, known as intismeran autogene and formerly called mRNA-4157 or V940, is designed individually for each patient using genetic information from their tumour.
Researchers analyse genetic tumour variations and create an mRNA vaccine encoding neoantigens, which are proteins unique to the cancer cells and a promising target for cancer therapy.
The vaccine is then intended to “train” the immune system to recognise and destroy cells carrying those alterations.
Unlike preventive vaccines, such as the flu shot, cancer vaccines are therapeutic, meaning a patient receives it after a cancer diagnosis to treat the existing disease by boosting the body’s immune response, rather than giving it before to ward off future diseases.
Intismeran autogene was tested in combination with Keytruda – a checkpoint inhibitor that removes some of the immune system’s natural brakes, potentially enhancing the body’s anti-cancer response.
“The vaccine can be considered a personalised approach that is ‘tumour informed’, meaning that neoantigens from a patient’s individual tumour are used in the vaccine design,” said study senior investigator Janice Mehnert, MD, a Professor in the Department of Medicine at NYU Grossman School of Medicine.
“This is given with the anti-PD-1 therapy, which is more of an empiric and standardised approach to result in truly personalised therapy,” she added.
“We also show that this approach has benefits for toxicity,” said presenting author Matteo Carlino, BMedSc, MBBS, a medical oncologist at Westmead and Blacktown Hospitals, faculty member at Melanoma Institute Australia, and a clinical senior lecturer at The University of Sydney in Australia.
“Prior attempts to improve on single agent anti-PD1 with dual checkpoint inhibition led to higher rates of immune related toxicities (irAEs). Such toxicities are particularly concerning in the adjuvant setting. In our study the combination did not increase the rate of irAE, and was actually associated with a slightly lower rate or irAEs,” added Carlino.
What the study found
The phase 2b clinical trial – KEYNOTE-942, enrolled 157 patients with high-risk melanoma who had undergone surgery between 2019 and 2021.
After five years of follow-up, those receiving the Intismeran autogene plus Keytruda had a 59% lower risk of the cancer spreading to distant organs compared with those receiving Keytruda alone.
Notably, overall survival was 92.2% in the combination group versus 71.3% in the Keytruda-only group.
These results also build on earlier analyses showing the combination reduced the risk of recurrence or death by 49% at the five-year mark, consistent with previous three-year data reported in 2023.
Researchers reported that seven patients in each treatment group died during follow-up, most due to cancer. The safety profile appeared consistent with earlier analyses.
The findings add to growing evidence that personalised cancer vaccines could become an important part of melanoma treatment in the future.
Why the findings matter
Researchers say the data are encouraging because they suggest the immune response generated by the personalised vaccine may remain durable over time.
However, further research is still necessary. If larger trials confirm the findings, personalised vaccines could eventually become part of standard treatment for melanoma and potentially other cancers.
Researchers have already fully enrolled a phase 3 trial, known as INTerpath-001, which is evaluating Intismeran autogen in melanoma. In addition, there is also a series of other studies across non–small-cell lung cancer, renal cell carcinoma, and bladder cancer.
More trials necessary
Although the results are promising, the study was relatively small, and larger trials are still necessary before the treatment can be approved for routine clinical use.
Additionally, personalised vaccines also involve a complex manufacturing process, as each dose must be custom-built from an individual’s tumour sample. As such, this approach will also need to be affordable and efficient on a larger scale.
Jeff Coller, a Professor of RNA biology and therapeutics at Johns Hopkins University in Baltimore who wasn’t involved with this research, said the results show that “the vaccine is doing exactly what we hoped it would do”.
“It’s training the immune system to recognise the tumour signature long after the tumour has gone,” he told NBS News.
The melanoma vaccines were in development before the Covid pandemic, but the research builds on the significant advances made in mRNA technology over the past six years.
Mehnert said the results of a large-scale, phase 3 trial, which included 1 000 patients and expanded to Europe, will provide the real proof of whether personalised mRNA vaccines added to standard immunotherapy significantly reduce the risk of melanoma returning.
All of the patients in the larger trial have finished treatment, and Mehnert and her team are working on compiling the results.
But having promising five-year data from the study that was just published is still important, said Dr Ravi Amaravadi, a Professor of Medicine at the University of Pennsylvania Perelman School of Medicine, who specialises in melanoma patient care. Most cancers that are going to return do so in the first five years.
“If there is no recurrence within that time, we usually stop or slow down scanning,” said Amaravadi, who was not involved with the trial.
One advantage the vaccine appears to have over other therapies is low toxicity, said Dr Shailender Bhatia, Director of the melanoma team at Fred Hutch Cancer Centre in Seattle, who was not involved in the study.
“Generally what we have seen is that if we layer more drugs with immunotherapy, it causes more toxicity but not more benefit. So that is where the results of this trial are promising,” Bhatia said.
People in the trial reported similar side effects to those from mRNA Covid vaccines – flu-like symptoms including chills and headaches – that only lasted a couple of days.
Mehnert and her team found that people whose cancers did not return also had the most robust immune response post-vaccine, suggesting it is the vaccine that boosted recurrence-free survival over five years.
Study details
Intismeran Autogene Plus Pembrolizumab Versus Pembrolizumab Alone in High-Risk Resected Melanoma: 5-Year Update of the Randomised Phase 2b KEYNOTE-942 Study
Adnan Khattak, Matteo Carlino, Tarek Meniawy et al.
Published in Journal of Clinical Oncology on 1 June 2026
Abstract
Intismeran autogene (intismeran; formerly V940 or mRNA-4157) is an mRNA-based individualised neoantigen therapy. We report 5-year outcomes of intismeran plus pembrolizumab from the phase 2b KEYNOTE-942 study (NCT03897881). Eligible patients with resected stage IIIB‒IV cutaneous melanoma were randomized 2:1 to receive 9 doses of intramuscular intismeran 1 mg Q3W plus 18 doses of intravenous pembrolizumab 200 mg Q3W or 18 doses of intravenous pembrolizumab 200 mg Q3W. Primary endpoint was recurrence-free survival (RFS); secondary endpoints included distant metastasis-free survival (DMFS) and safety. Five-year analyses were descriptive. Among 157 randomised patients (intismeran plus pembrolizumab, n=107; pembrolizumab, n=50), median planned follow-up at data cutoff (December 15, 2025) was 60.3 (range, 50.5‒76.4) months. Intismeran plus pembrolizumab continued to prolong RFS (HR, 0.510; 95% CI, 0.294‒0.887) and DMFS (0.411; 0.200‒0.843), with a favorable trend in overall survival (0.471; 0.165‒1.345) versus pembrolizumab. Safety profile continued to be manageable, with no new safety signals. Intismeran plus pembrolizumab was associated with increased T-cell receptor clonality and novel clonotypes versus pembrolizumab; greater novel clone expansion was observed in patients without versus with recurrence in the combination arm. After 5 years’ follow-up, intismeran plus pembrolizumab demonstrated sustained, durable treatment benefits versus pembrolizumab alone in resected high-risk melanoma.
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