In clinical trials — melanoma phase 3 met its goals (ESMO, October 2026); not yet approved in the US, Europe or Japan Sources: ESMO 2026 phase 3 presentation, Lancet 2024, Nature 2025, trial registries
An mRNA cancer vaccine is a personalized treatment that delivers, as mRNA, the blueprint of mutant protein fragments found only in one patient’s tumor, helping immune cells learn that target and attack any remaining cancer cells. In an international phase 3 trial of 1,137 patients whose melanoma had been completely removed by surgery, adding the vaccine to the immunotherapy drug pembrolizumab lowered the risk of recurrence or death by 42% (presented at the European Society for Medical Oncology, ESMO, in October 2026). It is not yet approved, and patients can currently receive it through clinical trials in Japan and other countries.
How does an mRNA cancer vaccine work?
As cancer cells grow, mutations build up in their genes, and these mutations create small protein fragments that normal cells do not have. These fragments are called neoantigens. T cells, a type of immune cell, are meant to find and attack such “foreign markers”, but cancers have many ways of escaping this surveillance.
mRNA (messenger RNA) is a nucleic acid that carries the instructions telling a cell which protein to make. An mRNA cancer vaccine packs mRNA encoding the patient’s neoantigens into tiny fat bubbles called lipid nanoparticles and is injected into a muscle. Cells near the injection site use the blueprint to make and display the neoantigens, so the immune system learns the target and expands T cells that attack cancer cells carrying those markers. Because it aims to prevent an existing cancer from coming back rather than to prevent infection, it is also called a therapeutic vaccine.
Immune checkpoint inhibitors (PD-1 inhibitors) release the “brakes” that cancer places on immune cells. The vaccine points out the target and the checkpoint inhibitor releases the brakes, so most current trials use the two together. To see where mRNA sits within nucleic acid medicine as a whole, read Nucleic acid medicine and aptamers: getting the terms right.
How a personalized vaccine is made
- Surgery and tissue: tumor tissue removed at surgery is sent together with a normal blood sample. In the phase 3 trial, 17.3% of screened patients could not take part because the tumor sample was not sufficient, so it helps to check with your medical team before surgery how the tissue will be stored.
- Genetic analysis: the tumor and blood genomes are compared to find mutations present only in the cancer.
- Choosing targets: computer analysis selects up to 34 neoantigens most likely to trigger an immune response (for intismeran autogene).
- Manufacturing: the chosen targets are joined into a single mRNA strand to make a vaccine for that one patient. In the phase 3 trial, the vaccine was successfully made for more than 99% of patients assigned to it.
- Treatment: up to 9 intramuscular injections, one every 3 weeks, given alongside intravenous pembrolizumab. The full course lasts about one year.
Results in patients
The vaccine with the most data is intismeran autogene (mRNA-4157/V940), developed jointly by Moderna and Merck (known as MSD outside the US and Canada). Results have pointed in the same direction from phase 2 to phase 3.
| Trial | Patients | Vaccine + pembrolizumab | Pembrolizumab alone |
|---|---|---|---|
| KEYNOTE-942 (phase 2b, 157 patients) | High-risk stage III/IV melanoma after surgery | 18-month recurrence-free survival 79% | 62% |
| KEYNOTE-942, 5-year follow-up | Same as above | 5-year recurrence-free survival 68.8%, 5-year overall survival 92.2% | 49.1%, 71.3% |
| INTerpath-001 (phase 3, 1,137 patients) | Stage IIB to IV melanoma after surgery | 2-year recurrence-free survival 82.2%, 2-year distant metastasis-free survival 88.5% | 70.0%, 80.2% |
Sources: Weber JS et al., Lancet 2024 / J Clin Oncol 2026 abstract (5-year results) / ESMO 2026 LBA1 (phase 3). The 5-year overall survival figure is an exploratory analysis.
In phase 3, the hazard ratio for recurrence or death was 0.58 (a 42% lower risk) and for distant metastasis or death 0.62 (38% lower), both statistically significant. Median follow-up was 24.6 months, and overall survival follow-up is continuing. In the 5-year follow-up of the phase 2b trial, the reduction in recurrence risk held at around 49%, showing that the benefit is durable.
Results in patients are also emerging for other cancers. In a phase 1 pancreatic cancer trial at Memorial Sloan Kettering Cancer Center in the US, 8 of 16 patients who received a personalized mRNA vaccine (autogene cevumeran) after surgery developed vaccine-induced T cells. In these 8 patients, median recurrence-free survival had not been reached over a median follow-up of 3.2 years, compared with 13.4 months in non-responders. The vaccine-induced T cells had an estimated average lifespan of 7.7 years, suggesting long-lasting immune memory (Nature 2025).
Side effects and how they are managed
In phase 3, the symptoms more common with the added vaccine were fever (52.2%), injection-site pain (51.0%), fatigue (38.5%) and flu-like illness (25.4%). Most were reported to settle on their own and are managed with fever reducers and rest. Treatment-related grade 3 or higher side effects occurred in 14.2%, similar to pembrolizumab alone (13.4%). Thyroid, skin and bowel effects linked to immunotherapy are monitored as usual with regular blood tests and check-ups.
Where can patients receive it?
As of October 2026, mRNA cancer vaccines are not yet approved in the US, Europe or Japan. Moderna has mentioned the potential for approval in 2027; until then, clinical trials are the way to receive one.
- Melanoma: the phase 3 INTerpath-001 trial (NCT05933577) is also listed in Japan’s clinical trial registry, sponsored by MSD Japan (jRCT2041230169). Enrollment has already been completed.
- Lung cancer: an international phase 3 trial is under way for resectable stage II to IIIB non-small cell lung cancer, and National Cancer Center Hospital East in Japan lists itself as a participating site. Moderna is running nine phase 2 and 3 trials across several cancers, including three phase 3 trials in lung cancer.
- A “cancer vaccine” offered as self-pay care at Japanese clinics may be a different product from the trial vaccines above, so check the product name and approval stage first.
To compare with other immune-cell treatments, see CAR-NK vs CAR-T; for the scope of information from Japan, see Nucleic acid medicine & aptamers.
Questions to ask your doctor
- Is there an mRNA cancer vaccine trial in Japan or abroad that fits my cancer type and stage?
- Can the tumor tissue removed at surgery be stored so it can be used for genetic analysis?
- Can my current immunotherapy schedule be coordinated with a vaccine trial schedule?
- If I get a fever after an injection, which medicine should I take, and when should I contact the hospital?
Frequently asked questions
Is an mRNA cancer vaccine the same as a COVID-19 vaccine?
The technology of wrapping mRNA in lipid nanoparticles and injecting it into a muscle is the same. A COVID-19 vaccine carries the same viral protein blueprint for everyone, whereas a personalized cancer vaccine carries neoantigen blueprints chosen from one patient’s own tumor mutations.
Can the mRNA cancer vaccine be given on its own?
All trials with positive results so far gave the vaccine together with the immunotherapy drug pembrolizumab. The vaccine shows the immune system the target while the checkpoint inhibitor releases the immune brakes, so combination use is the standard design.
Which patients are eligible?
The phase 3 results so far concern melanoma patients at high risk of recurrence after their cancer was completely removed by surgery. Trials in lung cancer and other cancers are also under way with the goal of preventing recurrence after surgery.
When will mRNA cancer vaccines be approved?
The phase 3 trial met its goals and the developers are preparing for regulatory review; Moderna has mentioned the potential for approval in 2027. The exact timing depends on reviews by the US FDA, the European EMA and Japan’s PMDA.
Related: What is oncolytic virus therapy? · Aptamer vs antibody · NK cell therapy process
Sources
- Merck & Moderna — Phase 3 INTerpath-001 trial of intismeran autogene plus KEYTRUDA met endpoints of RFS and DMFS in completely resected stage IIB–IV melanoma (2026-08-19)
businesswire.com
Checked: 2026-10-25 - CancerNetwork — INTerpath-001 data detail survival, subgroup, and safety findings in melanoma (ESMO 2026, LBA1)
cancernetwork.com
Checked: 2026-10-25 - ESMO — Adjuvant mRNA-4157 plus pembrolizumab prolongs RFS versus pembrolizumab alone in patients with resected high-risk melanoma (Weber JS et al., Lancet 2024)
esmo.org
Checked: 2026-10-25 - Five-year KEYNOTE-942 results show durable benefit of intismeran plus pembrolizumab (J Clin Oncol 2026 abstract)
hmpgloballearningnetwork.com
Checked: 2026-10-25 - Sethna Z, Guasp P, Reiche C 외/et al., Balachandran VP. RNA neoantigen vaccines prime long-lived CD8+ T cells in pancreatic cancer. Nature 2025;639:1042–1051
doi.org/10.1038/s41586-024-08508-4
Checked: 2026-10-25 - Moderna — IR Insights: Recapping the Phase 3 INTerpath-001 results
modernatx.com
Checked: 2026-10-25 - ClinicalTrials.gov — A Clinical Study of Intismeran Autogene (V940) Plus Pembrolizumab in People With High-Risk Melanoma (V940-001, NCT05933577)
clinicaltrials.gov
Checked: 2026-10-25 - jRCT2041230169 — V940 + pembrolizumab vs placebo + pembrolizumab adjuvant therapy in high-risk melanoma (MSD K.K.) (Japanese source)
jrct.niph.go.jp
Checked: 2026-10-25 - National Cancer Center Hospital East — Phase 3 international trial K1645 (V940, resectable non-small cell lung cancer) (Japanese source)
ncc.go.jp
Checked: 2026-10-25
Written by the FTH editorial team. Sources checked 2026-10-25 · Medical review: not applicable
This article is general information based on public sources and does not replace diagnosis or treatment. Please discuss treatment decisions with your medical team.
